International Journal of Molecular Veterinary Research 2024, Vol.14 http://www.animalscipublisher.com/index.php/ijmvr © 2024 AnimalSci Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved.
International Journal of Molecular Veterinary Research 2024, Vol.14 http://www.animalscipublisher.com/index.php/ijmvr © 2024 AnimalSci Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved. AnimalSci Publisher is an international Open Access publisher specializing in animal science, and veterinary-related research registered at the publishing platform that is operated by Sophia Publishing Group (SPG), founded in British Columbia of Canada. Publisher AnimalSci Publisher Editedby Editorial Team of International Journal of Molecular Veterinary Research Email: edit@ijmvr.animalscipublisher.com Website: http://www.animalscipublisher.com/index.php/ijmvr Address: 11388 Stevenston Hwy, PO Box 96016, Richmond, V7A 5J5, British Columbia Canada International Journal of Molecular Veterinary Research (ISSN 1927-5331) is an open access, peer reviewed journal published online by AnimalSci Publisher, an independent publishing platform in life science, based British Columbia of Canada. The journal is publishing all the latest and outstanding research articles, letters and reviews in all aspects of molecular veterinary research, containing diseases and disease vectors of livestock and wildlife around the world, the epidemiology, diagnosis, case report, prevention and treatment of medical conditions of domestic at molecular level, as well as the biomedical procedures that based on their health. Meanwhile we also publish the articles related to basic research, such as anatomy and histology, which are fundamental to molecular technique’s innovation and development. All the articles published in International Journal of Molecular Veterinary Research are Open Access, and are distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. AnimalSci Publisher uses CrossCheck service to identify academic plagiarism through the world’s leading plagiarism prevention tool, iParadigms, and to protect the original authors’ copyrights.
International Journal of Molecular Veterinary Research (online), 2024, Vol.14, No.1 ISSN 1927-5331 http://www.animalscipublisher.com/index.php/ijmvr © 2024 AnimalSci Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved. Latest Content Overcoming Feline Calicivirus: Modern Treatment Methods and Comprehensive Management Strategies Zhaolin Wang, Xiaofang Lin International Journal of Molecular Veterinary Research, 2024, Vol. 14, No. 1, 1-8 Enhancing Dairy Cow Milk Fat Synthesis Genes with CRISPR-Cas9 Technology to Increase Dairy Product Yield BoYang International Journal of Molecular Veterinary Research, 2024, Vol. 14, No. 1, 9-16 Long-Term Impact of Feline Calicivirus (FCV): From Transmission Dynamics to Disease Management Zhaolin Wang, Xiaofang Lin International Journal of Molecular Veterinary Research, 2024, Vol. 14, No. 1, 17-22 Research on the Threat of H5N1 Avian Influenza Virus to Chicken Health and Its Molecular Mechanisms Siping Zhang, Haiyong Chen International Journal of Molecular Veterinary Research, 2024, Vol. 14, No. 1, 23-31 Study on the Effect of Temperature on Epigenetic Marks in Mice Zhenni Lu International Journal of Molecular Veterinary Research, 2024, Vol. 14, No. 1, 32-39
International Journal of Molecular Veterinary Research 2024, Vol.14, No.1, 1-8 http://animalscipublisher.com/index.php/ijmvr 1 Clinical Case Review Open Access Overcoming Feline Calicivirus: Modern Treatment Methods and Comprehensive Management Strategies Wang Zhaolin1, , Lin Xiaofang2 1 Ruipai Pet Hospital, Sanya, 572000, Hainan, China 2 Tropical Animal Medicine Center of Hainan Tropical Agricultural Resources Research Institute, Sanya, 572025, Hainan, China Corresponding author email: 745457309@qq.com International Journal of Molecular Veterinary Research, 2024, Vol.14, No.1 doi: 10.5376/ijmvr.2024.14.0001 Received: 10 Nov., 2023 Accepted: 15 Dec., 2023 Published: 01 Jan., 2024 Copyright © 2024 Wang and Lin, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Wang Z.L., and Lin X.F., 2024, Overcoming feline calicivirus: modern treatment methods and comprehensive management strategies, International Journal of Molecular Veterinary Research, 14(1): 1-8 (doi: 10.5376/ijmvr.2024.14.0001) Abstract This study comprehensively explores modern treatment methods and comprehensive management strategies for feline calicivirus (FCV). By systematically introducing the basic characteristics, epidemiology, and significance of FCV, the research aims and expectations are elucidated. It also provides a detailed analysis of the basic biology and pathology of FCV, including virus structure, genetic diversity, infection pathways, clinical manifestations, and pathological mechanisms. In terms of modern therapeutic methods, the study delves into antiviral treatments, supportive therapy, and treatment strategies for special cases. It focuses on the types and mechanisms of antiviral drugs, the importance of supportive treatment, and considerations for treatment in cases of chronic infection and multi-cat environments. The research showcases the treatment process and outcomes of FCV through a clinical case, thoroughly discussing preventive and comprehensive management strategies. This includes the types, effects, and limitations of vaccines, preventive measures, health management of cat populations, and the importance of educating pet owners.Finally, the study summarizes the current challenges faced in treating and managing FCV and anticipates possible future treatment strategies and health management systems. The goal is to provide valuable reference for veterinary practitioners, promoting a deeper understanding and effective treatment of FCV. Keywords Feline calicivirus (FCV); Modern treatment methods; Comprehensive management strategies; Clinical case studies; Prevention and control Feline calicivirus (FCV) is a major pathogen affecting the health of cat populations, belonging to the Caliciviridae family, a non-enveloped, single-stranded positive-sense RNA virus. It is primarily transmitted through respiratory secretions, saliva, or direct contact, exhibiting high infectivity and widespread prevalence. Common symptoms in cats infected with FCV include oral ulcers, respiratory symptoms, fever, and even pneumonia (Wang, 2023; Gui, 2023). It is worth noting that FCV displays a certain degree of variability, adding complexity to the prevention and control of the disease. The epidemiological characteristics of FCV in cat populations are significant. It not only affects domestic cats but also spreads widely among feral cats, posing a serious public health concern. Although most infections manifest as mild to moderate symptoms, severe cases can occur, leading to fatal diseases, especially in kittens, elderly cats, or immunocompromised cats (Hofmann-Lehmann et al., 2022). Additionally, FCV infections may result in widespread transmission within cat populations, presenting a risk to overall group health. In the face of this challenge, researchers urgently need a deeper understanding of FCV infection mechanisms and exploration of more effective clinical treatment methods. Currently, FCV treatment relies mainly on symptom support and adjunctive therapy, lacking specific antiviral treatment methods. Therefore, research and development of new antiviral strategies, optimization of supportive treatment measures, and the establishment of comprehensive infection management and prevention systems are crucial for controlling and reducing the impact of FCV infections (Guo et al., 2022). This study aims to comprehensively analyze the current clinical treatment status of FCV, explore modern treatment methods, and develop integrated management strategies. Through systematic literature reviews and case
International Journal of Molecular Veterinary Research 2024, Vol.14, No.1, 1-8 http://animalscipublisher.com/index.php/ijmvr 2 analyses, we hope to provide comprehensive treatment and prevention guidance for FCV infections, reducing the negative impact on cat population health and provide scientific basis and practical guidelines for veterinary clinical practice. Through this work, we hope to contribute to overcoming FCV infection, protecting animal welfare, and public health safety. 1 Basic Biology and Pathology of FCV 1.1 Structure and genotypic diversity of FCV Feline calicivirus (FCV), a member of the Caliciviridae family, is a non-enveloped virus with a particle diameter of approximately 30-40 nm. The genome of FCV consists of a single-stranded positive-sense RNA, with a length of about 7.7 kilonucleotides, encoding various viral proteins, including structural and non-structural proteins. One of its distinctive features is the diversity in genotypes, primarily attributed to the high error rate of the RNA-dependent RNA polymerase, leading to frequent occurrences of mutations and recombination events. This genetic diversity enables FCV to adapt to different hosts and environmental conditions, posing challenges to vaccine development and virus control. 1.2 Infection pathways and clinical manifestations FCV is primarily transmitted through direct contact, including saliva, eye secretions, and nasal secretions of infected cats, as well as contact with contaminated objects (such as food bowls, bedding). Airborne droplets may also serve as a potential transmission route. Typical clinical manifestations include acute upper respiratory tract disease, oral ulcers, conjunctivitis, and nasal discharge. While most cats exhibit mild symptoms, in immunocompromised or unvaccinated cats, FCV can lead to more severe diseases, including pneumonia, systemic viral infections, and even death. 1.3 Pathological mechanisms FCV infection initially occurs in the epithelial cells of the oral cavity or upper respiratory tract. Virus particles enter cells by binding to receptors on the host cell surface, initiating the replication cycle (Li et al., 2022). Viral replication results in cell damage and death, triggering an inflammatory response. Behind oral ulcers and upper respiratory symptoms lies the disruption of mucosal epithelial cells and the integrity of submucosal capillaries by the virus, leading to local tissue inflammation and ulcer formation. In addition to direct cell damage, FCV can further contribute to tissue injury by activating the host's immune response. For instance, the infiltration of inflammatory cells and the release of cytokines can exacerbate local and systemic inflammatory reactions. Interestingly, FCV also demonstrates some immune escape capabilities, such as evading host neutralizing antibody responses through mutation (Tian et al., 2020). Moreover, the virus may induce latent infections in some hosts, leading to sustained immune activation and chronic inflammatory states (Wang, 2023). The pathological mechanisms of FCV are diverse and complex, and the unique viral structure and genetic diversity present additional challenges for therapy development and disease control. Therefore, a profound understanding of these fundamental biological and pathological mechanisms is crucial for the development of effective prevention and treatment strategies. 2 Modern Treatment Approaches 2.1 Antiviral therapy The primary challenge in treating feline calicivirus (FCV) lies in its high variability and the lack of specific drugs. Currently, antiviral drug use primarily focuses on two categories: nucleoside analogs and RNA polymerase inhibitors. Nucleoside analogs, such as ribavirin, disrupt the virus's replication process by mimicking nucleotides in viral RNA. RNA polymerase inhibitors, on the other hand, act by inhibiting a key enzyme in virus replication. These drugs can interfere with virus replication at different stages of the viral lifecycle, thereby alleviating symptoms (Wang, 2023).
International Journal of Molecular Veterinary Research 2024, Vol.14, No.1, 1-8 http://animalscipublisher.com/index.php/ijmvr 3 Although antiviral drugs are theoretically effective, they face various limitations in practical application. Most antiviral drugs are designed for human viruses, and their efficacy against FCV may be limited. Additionally, the high variability of FCV may lead to the rapid development of drug resistance. Therefore, while these drugs can be part of a treatment plan, their effectiveness and safety evaluation require a comprehensive assessment of individual responses and clinical presentations. As our understanding of FCV biology deepens, novel antiviral treatment strategies are under development. For instance, approaches based on RNA interference (RNAi) are being explored to specifically target and degrade viral RNA, representing a potentially more precise treatment method. Simultaneously, researchers are also attempting to develop more effective vaccines to prevent infection or alleviate symptoms. 2.2 Supportive therapy FCV infection in cats often accompanies reduced appetite and dehydration symptoms. Therefore, proper nutrition and fluid support are crucial components of treatment. Nutritional support should include high-quality proteins, sufficient calorie intake, and essential vitamins and minerals. Regarding fluid therapy, intravenous or subcutaneous fluid administration may be necessary based on the specific condition of the affected cat to correct dehydration and maintain electrolyte balance. FCV infection commonly leads to painful symptoms such as oral ulcers in cats. Appropriate pain relief measures, such as the use of opioid medications or non-steroidal anti-inflammatory drugs (NSAIDs), can significantly improve the cat's comfort (Figure 1). However, it is essential to note that the use of these drugs must be under veterinary guidance to avoid adverse reactions. Figure 1 Oral medication In the treatment of FCV, immunomodulators also play a significant supportive role (Kulenkova et al., 2020). For example, interferons can enhance the host immune system's response to the virus. Additionally, some immune boosters like L-lysine are believed to contribute to managing FCV infections. However, the long-term efficacy and side effects of these drugs require further clinical research for clarification. 2.3 Treatment strategies in special cases For cats with chronic FCV infection, a comprehensive and long-term treatment plan is necessary. This may include regular clinical monitoring, personalized drug treatment plans, and strict hygiene control measures. The key to long-term management lies in regularly assessing changes in the cat's condition and adjusting the treatment plan accordingly.
International Journal of Molecular Veterinary Research 2024, Vol.14, No.1, 1-8 http://animalscipublisher.com/index.php/ijmvr 4 In multi-cat environments, such as shelters or catteries, the complexity of FCV management significantly increases. In such situations, in addition to individual treatment for infected cats, group-level control measures must be implemented. This includes effective isolation policies, maintaining environmental hygiene, regular disinfection, and promoting a comprehensive vaccination schedule. Through these comprehensive measures, the risk of disease spread within the population can be effectively reduced. 3 Prevention and Comprehensive Management Strategies 3.1 Types, efficacy, and limitations of vaccines Vaccines for feline calicivirus (FCV) mainly come in two types: inactivated vaccines and attenuated live vaccines. Inactivated vaccines are generally considered safer but may require boosters to enhance immune effectiveness. Attenuated live vaccines can induce a stronger immune response, but safety concerns may arise in very rare cases. Although FCV vaccines cannot provide 100% protection, they significantly reduce the risk of infection and alleviate symptoms post-infection. The primary goal of vaccines is to prevent severe diseases caused by FCV, and their effectiveness against viral variants may be limited. Due to the high genetic diversity of FCV, existing vaccines may not offer sufficient protection against all prevalent strains. Additionally, the effect of vaccines on clearing or reducing virus shedding in carriers is limited. Therefore, even vaccinated cats may potentially become carriers of the virus (Bergmann et al., 2019). 3.2 Control measures (e.g., isolation, disinfection) Upon detecting FCV infection in a cat population, infected cats should be promptly isolated from healthy cats (Figure 2). The isolation period should last at least for a period of time after clinical symptoms completely disappear. Furthermore, veterinarians and cat caregivers should take appropriate personal protective measures, such as changing gloves and clothing, to minimize the risk of virus transmission when handling different cats. Figure 2 Isolation of sick cats (Source: this hospital) FCV is relatively stable in the environment, emphasizing the importance of environmental disinfection. Regularly clean cat living areas, including food and water containers, sleeping mats, and toys, using effective disinfectants (such as chlorides or peroxides). Care should be taken in selecting and using disinfectants to avoid health risks to cats. 3.3 Health management for cat populations Regular health checks for cat populations (Dávila et al., 2018) and early identification and isolation of infected cats are crucial for controlling FCV spread. Besides visual and behavioral observations, routine physical examinations and laboratory tests (such as blood and urine analyses) are essential.
International Journal of Molecular Veterinary Research 2024, Vol.14, No.1, 1-8 http://animalscipublisher.com/index.php/ijmvr 5 Ensure that each cat receives adequate nutrition and resides in a clean, comfortable environment. Sufficient nutrition and good living conditions can enhance the overall health and immunity of cats, thereby reducing the incidence of diseases. 3.4 Importance of educating pet owners Awareness and understanding of FCV by pet owners are crucial. Through education, informing them about the modes of FCV transmission, symptoms, preventive measures, and control strategies can help minimize disease spread. Simultaneously, educating pet owners about the importance of regular vaccination for their cats is crucial. Even though vaccines cannot provide complete protection, they remain an effective means of preventing severe diseases and reducing virus transmission. Educating pet owners on how to properly care for their cats, including providing a balanced diet, maintaining a clean living environment, and scheduling regular veterinary check-ups, contributes to raising the overall health level of cats and reducing the occurrence of diseases. By implementing these prevention and comprehensive management strategies, the spread of FCV can be effectively controlled, minimizing the impact of the disease on the health of cat populations. 4 Management of Secondary Infections 4.1 Identification and treatment of secondary bacterial or fungal infections Secondary infection is usually the main reason for the complexity of FCV infections. These infections, especially common in cats with compromised immune systems (Hofmann-Lehmann et al., 2022), may be caused by bacteria or fungi. It is crucial to recognize early signs of these secondary infections, such as persistent fever, difficulty breathing, worsening oral ulcers, coughing, or increased eye discharge. Upon identification of a secondary infection, immediate treatment should commence. This may involve antibiotics or antifungal therapy targeted at the specific infection. The choice of appropriate medications often relies on the results of bacterial cultures and drug sensitivity testing. Simultaneously, reinforcing supportive care, such as nutritional support and appropriate hydration, is vital for recovery. 4.2 Key complications to focus on FCV infection can lead to severe upper respiratory complications. In the context of secondary infections, these complications may worsen, including pneumonia, bronchitis, or tracheitis. Identifying these symptoms and promptly administering appropriate treatment are key to alleviating the condition and improving chances of recovery. FCV infections commonly result in oral issues, such as oral ulcers (Gao et al., 2022). In cases of secondary infections, these problems may escalate, causing severe pain and difficulty in eating. Maintenance of oral hygiene, along with the use of analgesics and anti-inflammatory drugs when necessary, is crucial for mitigating these complications. 4.3 Monitoring and long-term management strategies Regular health monitoring is crucial for cats that have previously experienced FCV infection with secondary infections. This includes routine physical examinations, blood tests, and imaging studies to ensure there is no development of potential complications. For cats with chronic symptoms or frequent recurrences, long-term management strategies may be necessary. This could involve ongoing administration of specific medications, regular veterinary visits, and special adjustments to the living environment, such as reducing sources of stress, providing high-nutrient-value food, and maintaining good environmental hygiene. Pet owners play a crucial role in managing secondary infections. Educating them to recognize signs of recurrence, understanding the importance of disease management, and encouraging regular follow-ups and treatments as advised by the veterinarian are essential.
International Journal of Molecular Veterinary Research 2024, Vol.14, No.1, 1-8 http://animalscipublisher.com/index.php/ijmvr 6 Through these comprehensive strategies for managing secondary infections, complications can be effectively controlled, improving the quality of life for cats. Simultaneously, it provides support and guidance to pet owners in addressing this challenge collaboratively. 5 Successful Treatment Case Study 5.1 Case description Kangkang, a typical Chinese LiHua cat, is housed at the Hainan Tropical Agriculture Resources Research Institute. He resides in a 400-square-meter indoor space on the third floor of the institute's office building. Kangkang is a male cat, born on July 17, 2020, and has been neutered. Despite receiving complete vaccinations and regular deworming, he exhibited symptoms such as hematuria, weight loss, oral ulcers, and gingival edema on October 22, 2023. His weight decreased from 7.5 kilograms to 6.6 kilograms. Preliminary examination revealed abdominal tenderness when touching Kangkang's abdomen, and there was noticeable swelling in the oral and pharyngeal regions. The diagnostic process involved clinical symptom observation and a five-fluorescent PCR test for feline respiratory diseases. The results indicated that Kangkang was infected with a cup-shaped virus, with a Ct value of 20.5, confirming a positive reaction. 5.2 Analysis of the treatment process The treatment plan encompassed several aspects: Initial assessment, including a comprehensive physical examination and evaluation of vital signs and overall health. Laboratory tests, including CT scans, blood routine, urinalysis, and specific FCV detection. Clinical treatment, involving analgesic, anti-inflammatory therapy, antiviral treatment targeting FCV, and concurrent supportive care. 5.3 Treatment methods employed Bayer Baytril Injection: Dosage of 1 mL, subcutaneous injection, once daily. Meloxicam: Dosage of 1 mL, subcutaneous injection, once daily. Zhongke Baiken Cat Interferon: 1.5 million U, subcutaneous injection, once daily. Kuru Oral Antimicrobial Spray: Oral spray, three times daily. The master of calicivirus/Lysozyme: Targeted genetic engineering, oral administration, twice daily, one capsule each time. High-nutrient wet food: To support Kangkang's overall nutritional needs. 5.4 Special management strategies Kangkang was isolated after discharge to prevent direct contact with other pets, reducing the risk of disease transmission. Additionally, continued oral administration of the master of calicivirus for two treatment courses (8 days each) was prescribed to consolidate the treatment effect. 5.5 Prevention and management of secondary infections During Kangkang's treatment, special attention was given to monitoring and preventing potential secondary infections. The occurrence of secondary infections was successfully avoided through regular examinations and timely treatment adjustments. 5.6 Treatment outcome Following Kangkang's discharge on November 7, 2023, there was a noticeable improvement in his overall health. The results of the five fluorescent PCR tests for the respiratory tract conducted on December 7, 2023 were negative, indicating the success of the treatment. 5.7 Academic and clinical significance of the case This case demonstrates the effectiveness of a comprehensive treatment approach for FCV infection in a clinical setting. It underscores the importance of early diagnosis, comprehensive treatment plans, and strict management strategies in controlling FCV infections. Furthermore, the case proves that high-risk cats, such as those with other health issues, can achieve positive treatment outcomes with appropriate care.
International Journal of Molecular Veterinary Research 2024, Vol.14, No.1, 1-8 http://animalscipublisher.com/index.php/ijmvr 7 5.8 Insights into existing treatment strategies from the case Kangkang's case provides valuable practical experience for the treatment of FCV infections. It serves as a crucial reference for similar cases in the future, particularly in the application of comprehensive treatment strategies, the design of individualized treatment plans, and the management of preventing secondary infections. Additionally, this case highlights the importance of communication between veterinarians and pet owners to ensure the smooth implementation of treatment plans and timely tracking of the pet's condition. 6Summary Feline calicivirus (FCV), as a common yet complex viral disease in cats, poses multiple challenges in its treatment and management. The widespread use of antiviral drugs has led to an increasing resistance of FCV to these medications. Current vaccines do not provide complete prevention against all FCV strains, and their effectiveness against certain variants is limited (Zheng et al., 2022). The high variability of FCV complicates treatment and prevention strategies. In multi-cat environments, managing virus transmission, reducing stress, and minimizing conflicts present additional challenges. Insufficient awareness among pet owners about FCV may result in improper disease management and treatment failures. Despite the numerous challenges in treatment, technological advancements have introduced new therapeutic strategies and research directions for FCV. The development of gene editing technologies such as CRISPR offers possibilities for precise targeting and repairing of viral genes. Future researchers can explore novel antiviral drugs, especially those targeting FCV-specific mechanisms, to overcome existing drug resistance. Developing broader and more effective vaccines, particularly those capable of addressing various mutant strains, is essential (Lu et al., 2018). Researching new immunomodulatory methods to enhance host immune responses and resistance to FCV is also crucial. Creating comprehensive treatment strategies that integrate drug therapy, immune modulation, and optimized management measures is an avenue for exploration. In the future, with the collaboration of technology and interdisciplinary efforts, the development and utilization of integrated health management systems seem promising. Researchers can explore the development of intelligent health monitoring tools, such as wearable devices, for real-time monitoring of a cat's health. Utilizing big data and artificial intelligence, personalized treatment and management plans can be formulated for each cat. Establishing a comprehensive platform for pet health education can enhance pet owners' disease awareness and management skills. Promoting collaboration among veterinarians, researchers, and technology developers will collectively drive the advancement of FCV treatment and prevention technologies. In conclusion, although the current treatment and management of FCV face various challenges, there is reason to anticipate more effective control and treatment of this disease in the future, thanks to the progress in science and technology and the deepening collaboration across multiple disciplines. References Bergmann M., Speck S., Rieger A., Truyen U., and Hartmann K., 2019, Antibody response to feline calicivirus vaccination in healthy adult cats, Viruses, 11(8): 702. https://doi.org/10.3390/v11080702 PMid:31370359 PMCid:PMC6723298 Dávila I., Domínguez-Ortega J., Navarro-Pulido A., Alonso A., Antolin-Amerigo D., González-Mancebo E., Martín-García C., Núñez-Acevedo B., Prior N., Reche M., Rosado A., Ruiz-Hornillos J., Sánchez M.C., and Torrecillas M., 2018, Consensus document on dog and cat allergy, Allergy, 73(6): 1206-1222. https://doi.org/10.1111/all.13391 PMid:29318625 Gao C.X., Chen B.J., Mi J., Han J.J., Lian S.C., Ma W.R., 2022, Epidemiological investigation and analysis of feline calicivirus in Xi’an, Chinese Journal of Veterinary Medicine, 58(3): 101-105. Gui Y.P., Liu J., Bai Y.L., Wang J., and Zhao H.J., 2023, Research progress on the characteristics of virulent systemic feline calicivirus, Chinese Journal of Virology, 39(4): 1093-1098. Guo Y.B., Liu H.K., Wang Q, Yi S.S., Niu J.T., Li D.L., Cui Z.D., Wang K., Shao H.Z., and Hu G.X., 2022, Assessment of the protective efficacy of a feline calicivirus inactivated vaccine using in vivo FCV CH-JL2 infection, Pak. Vet. J., 42(3): 328-333.
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International Journal of Molecular Veterinary Research 2024, Vol.14, No.1, 9-16 http://animalscipublisher.com/index.php/ijmvr 9 Research Report Open Access Enhancing Dairy Cow Milk Fat Synthesis Genes with CRISPR-Cas9 Technology to Increase Dairy Product Yield BoYang Qingyun Environmental Technology Co., Ltd, Shangyu, 312300, Zhejiang, China Corresponding author email: 1624454379@qq.com International Journal of Molecular Veterinary Research, 2024, Vol.14, No.1 doi: 10.5376/ijmvr.2024.14.0002 Received: 09 Nov., 2023 Accepted: 20 Dec., 2023 Published: 15 Jan., 2024 Copyright © 2024 Yang, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Yang B., 2024, Enhancing dairy cow milk fat synthesis genes with CRISPR-Cas9 technology to increase dairy product yield, International Journal of Molecular Veterinary Research, 14(1): 9-16 (doi: 10.5376/ijmvr.2024.14.0002) Abstract This study explores the prospects and potential impacts of using CRISPR-Cas9 technology to improve the genes involved in milk fat synthesis in cows, aiming to increase dairy product yield. Dairy products hold a significant position in global diets, making it an urgent challenge to enhance dairy product production. Milk fat synthesis genes in cows play a crucial role in both the quality and quantity of dairy products. CRISPR-Cas9 technology, as an efficient and precise gene editing tool, provides a powerful instrument for improving cow genetics. By precisely editing genes related to milk fat synthesis, it is possible to enhance the milk fat synthesis capacity of cows, thereby increasing dairy product yields. Gene-edited cows also have the potential to improve milk fat quality, reduce environmental impact, enhance food safety, and bolster the sustainability of the dairy industry. However, gene editing raises ethical and legal concerns that require careful consideration. Ensuring safety and ethical compliance is a key challenge in future research and applications. In summary, the prospects for using CRISPR-Cas9 technology to improve cow milk fat synthesis genes are promising and have the potential to make significant contributions to meeting the growing global demand for dairy products. Keywords CRISPR-Cas9 technology; Cow; Milk fat synthesis; Dairy product yield; Gene editing Dairy products have long been a crucial part of human diet, offering rich nutritional value and delightful flavors. The dairy industry holds significant economic and social importance globally, providing not only high-quality proteins, fats, and vitamins to humans but also generating employment and economic opportunities for rural communities and agricultural economies, effectively supporting the sustainable development of rural society. However, the dairy industry faces growing demands, necessitating continuous improvement in both the quantity and quality of dairy products to meet global market needs. Lipid synthesis plays a vital role in dairy production, influencing not only the fat content but also the taste and texture of dairy products (Petitclerc et al., 2000). The regulation of lipid synthesis involves various factors such as diet, genetics, and environment. Nevertheless, the fundamental regulatory mechanism lies in gene control, where the genes related to lipid synthesis in cows play a crucial role. Therefore, enhancing the lipid synthesis genes in cows holds the potential to enhance dairy product yield and quality. CRISPR-Cas9 technology stands as a powerful gene-editing tool, widely applied in fields such as medicine, agriculture, and biological research, providing unprecedented tools and opportunities for gene editing. In the medical field, it has been used to treat various genetic diseases, including cancer (Ma et al., 2023). In the field of agriculture, CRISPR-Cas9 technology has successfully been employed to improve plant varieties, enhancing resistance, yield, and quality (Hou et al., 2023). Despite the critical role of lipid synthesis in the dairy industry, the regulatory mechanisms of lipid synthesis remain not fully understood. This uncertainty hinders researchers from effectively improving the lipid synthesis process in cows. In the rapidly evolving dairy market, this slow progress is no longer practical. Therefore, the rapid and precise improvement of lipid synthesis genes in cows has become a significant issue. The emergence of gene-editing technology brings new opportunities to address this problem. Through CRISPR-Cas9 technology, researchers have the potential to quickly and accurately improve the lipid synthesis genes in cows, thereby enhancing the yield and quality of dairy products. The application of this technology in cow breeding holds immense potential, but whether it can successfully achieve this goal and whether it can have a positive impact on the dairy industry still requires in-depth research and validation.
International Journal of Molecular Veterinary Research 2024, Vol.14, No.1, 9-16 http://animalscipublisher.com/index.php/ijmvr 10 This study aims to review the application of CRISPR-Cas9 technology in improving lipid synthesis genes in cows, analyzing its potential benefits and challenges, and exploring its prospects in the field of dairy production. The study will delve into the genes related to lipid synthesis in cows, the principles of CRISPR-Cas9 technology, and how this technology can be applied to cow gene editing. It will also focus on successful cases in this field and potential future trends, contributing to the sustainable development and innovation in the agricultural sector. To provide comprehensive information on this cutting-edge technology to the academic and industrial communities through in-depth research and review, in order to promote further research and application in the field of cow gene editing. 1 Importance of Dairy Cow Milk Fat Synthesis Genes 1.1 Functions of milk fat synthesis-related genes The genes related to milk fat synthesis play a crucial role in the production and quality of dairy products. These genes encode various fatty acid synthesis enzymes and related proteins, controlling the types and amounts of fats in milk. Among them, three main genes are ACACA, FASN, and SCD, playing key roles in dairy cow milk fat synthesis (Kęsek-Woźniak et al., 2023). The gene ACACA encodes Acetyl-CoA carboxylase, a critical enzyme in the fatty acid synthesis process. This process typically begins with tyrosine in milk, undergoes multiple biochemical reactions, and eventually synthesizes fatty acids. Acetyl-CoA carboxylase is the first key enzyme in this synthesis pathway, participating in the conversion of tyrosine in milk into lactic acid, further transforming into lactic acid ethyl ester, ultimately forming fatty acids. Improving the function of the ACACA gene can enhance the efficiency of this synthesis pathway, thereby increasing dairy product yield. The FASNgene encodes Fatty Acid Synthase, a key player in fatty acid synthesis. Enhancing FASNfunction can increase the rate of fatty acid production, crucial for improving the efficiency of milk fat synthesis. The efficiency of milk fat synthesis is closely related to the quality and quantity of dairy products. By increasing the efficiency of milk fat synthesis, cows can produce more high-quality fats, thus improving the flavor and texture of dairy products. The SCD gene encodes Stearoyl-CoA Desaturase, involved in converting saturated fatty acids into unsaturated fatty acids. Unsaturated fatty acids play a vital role in dairy products as they contribute to human health by reducing cholesterol levels and lowering the risk of cardiovascular diseases. Regulating the SCD gene can enhance the synthesis of unsaturated fatty acids, improving the nutritional value of dairy products. The functions of dairy cow milk fat synthesis-related genes are crucial for the production and quality of dairy products. By improving the functions of these genes, it is possible to increase the yield and quality of milk fat, meeting the growing market demand and providing consumers with healthier and tastier dairy products. However, achieving these goals requires continued research and technological improvements to fully unlock the potential of dairy cow milk fat synthesis genes. 1.2 Relationship between dairy product quality and quantity The quality and quantity of dairy products are closely related, and the functions of dairy cow milk fat synthesis genes have a direct and profound impact on both aspects. Improving milk fat synthesis genes can significantly increase the production of dairy products. Fat is one of the essential components of dairy products, and its content determines the yield of dairy products. The biosynthesis process of fatty acids is the core of milk fat synthesis, and dairy cow milk fat synthesis genes encode enzymes and proteins related to fatty acid synthesis. By improving the functions of these key genes, the synthesis rate of fatty acids can be increased, allowing cows to produce more milk fat. This not only increases the overall production of dairy products but also helps meet the growing market demand for dairy products, thereby enhancing the economic benefits of agriculture. Improvements in milk fat synthesis genes also have a crucial impact on the quality of dairy products. The fatty acid composition in milk fat is one of the key factors determining the quality of dairy products. Different types
International Journal of Molecular Veterinary Research 2024, Vol.14, No.1, 9-16 http://animalscipublisher.com/index.php/ijmvr 11 and proportions of fatty acids directly affect the taste, texture, and nutritional value of dairy products (Figure 1) (Chen et al., 2004). For example, the content of unsaturated fatty acids can affect the taste of butter, while the content of saturated fatty acids can influence the texture and meltability of cheese. By regulating milk fat synthesis genes, a more precise fatty acid composition can be achieved to meet the quality standards of different types of dairy products and consumer preferences. Figure 1 Dairy products Improvements in milk fat synthesis genes also help increase the stability of milk fat, reducing oxidation and quality deterioration. This is crucial for extending the shelf life of dairy products and reducing food waste. By reducing oxidative reactions, milk fat can maintain a fresher and more stable state for a longer period, ensuring high quality during the distribution and sales of dairy products. The functions of dairy cow milk fat synthesis genes have a direct impact on the quality and quantity of dairy products, which is of great significance to agriculture and the food industry. Further research into gene editing and related technologies can better meet the growing market demand, providing higher quality and more diverse dairy products while ensuring the sustainability and economic benefits of food production. 1.3 Limitations of existing research Despite the widely recognized importance of dairy cow milk fat synthesis genes, there are still some limitations in current research aimed at improving these genes. Although CRISPR-Cas9 technology has achieved some success in dairy cow gene editing, there are still technical challenges. While CRISPR-Cas9 technology is highly accurate in targeted gene editing, its editing efficiency may not be sufficient for the needs of agricultural production when applied on a large scale. Improving gene editing technology to enhance editing efficiency remains an urgent task to ensure the desired gene changes in dairy cows. Precision is also a concern. In the CRISPR-Cas9 editing process, non-specific gene mutations or unexpected side effects may occur, posing potential risks to the health and productivity of dairy cows. Therefore, ensuring the accuracy and safety of editing is crucial. The issues of time and cost in gene editing also need to be considered. The high cost and cumbersome operating procedures may limit the feasibility of large-scale gene editing, especially for small dairy farms. The genetic diversity of the dairy cow population is crucial for maintaining the long-term stability and adaptability of the population. However, gene-edited cows may lead to a reduction in genetic diversity. Introducing specific gene edits may cause certain genotypes of cows to proliferate widely in the population, reducing genetic diversity. This could make cows more vulnerable to future environmental changes and disease pressures, as reduced genetic
International Journal of Molecular Veterinary Research 2024, Vol.14, No.1, 9-16 http://animalscipublisher.com/index.php/ijmvr 12 diversity lowers population adaptability. Irreversible mutations may occur during the gene editing of cows, potentially having long-term effects on genetic diversity. Therefore, measures need to be taken to monitor and protect the genetic diversity of the dairy cow population to prevent unexpected negative consequences. The importance of dairy cow milk fat synthesis genes in dairy product production cannot be ignored. By improving the functions of these genes, it is possible to increase the yield and quality of dairy products, meeting the growing market demand. However, current research still faces technical and practical challenges, requiring further investigation and exploration. 2 Application of CRISPR-Cas9 Technology in Agricultural Gene Editing 2.1 Development of CRISPR-Cas9 Understanding the historical development of CRISPR-Cas9 technology is crucial for a profound comprehension of its significance in agricultural gene editing. CRISPR (Clustered regularly interspaced short palindromic repeats) and Cas9 (CRISPR-associated protein 9) form a powerful duo that was initially discovered in the bacterial immune system, serving as a natural defense mechanism against viral invasions. Recognizing its potential for gene editing, researchers delved into in-depth studies of this system. The history of CRISPR technology dates back to the 1990s (Mojica et al., 1993), when researchers first observed a unique DNA sequence in bacterial genomes playing a crucial role in the bacterial immune response. However, at that time, understanding of the functionality and applications of these DNA sequences was limited. In 2012, Jennifer A. Doudna and Emmanuelle Charpentier proposed the concept of using CRISPR-Cas9 for gene editing, marking the beginning of extensive research in this field (Jinek et al., 2012). In the following years, researchers continually improved CRISPR-Cas9 technology, enhancing its accuracy and efficiency. These improvements included introducing different variants of Cas proteins, such as Cpf1, and refining the precision of editing tools. This discovery sparked widespread interest in the academic and biotechnological sectors, opening up a new avenue for scientists to precisely edit genomes. In the following years, CRISPR-Cas9 technology made significant progress and its application scope continued to expand. In the agricultural domain, CRISPR-Cas9 technology has been applied to enhance crops, endowing them with increased resistance to pests, drought, and diseases. Successful applications in other organisms have provided valuable experience and inspiration for applying CRISPR-Cas9 technology to to cow improvement, as similar principles and techniques can be applied to gene editing in different organisms, including cows (Edick et al., 2021). The historical development of CRISPR-Cas9 technology is an exhilarating journey, evolving from the accidental discovery in the bacterial immune system to a powerful gene-editing tool, bringing a huge revolution to the fields of biological science and agriculture. This progression establishes a solid foundation for the application of CRISPR-Cas9 in dairy cow improvement, providing valuable insights for future research and practical implementations. 2.2 Principles of gene editing Understanding the principles of gene editing is closely tied to comprehending the application of CRISPR-Cas9 technology in dairy cow improvement. Gene editing is a complex and precise engineering task (Horodecka and Düchler, 2021). Researchers initially select specific genes to edit, often related to milk synthesis, dairy product quality, and yield in the context of dairy cow improvement. To precisely edit target genes, researchers design guide RNA (gRNA) sequences capable of binding to specific regions of the target genes. The guide RNA directs the Cas9 protein to the vicinity of the target gene, ensuring that editing occurs at the correct location. Cas9 is an RNA-guided protein that, once bound to the guide RNA, can recognize and bind to specific sequences of the target gene. Once Cas9 binds to the target DNA, it induces a double-strand break. This marks the initiation of editing, as cells attempt to repair these breaks, usually through mechanisms like non-homologous end joining (NHEJ) or homology-directed repair (HDR). Ultimately, if the repair mechanism is successful or carefully designed by researchers, it may result in the desired genetic improvement, such as the insertion of specific gene sequences, removal of harmful gene mutations, or substitution of unfavorable genes (Figure 2).
International Journal of Molecular Veterinary Research 2024, Vol.14, No.1, 9-16 http://animalscipublisher.com/index.php/ijmvr 13 Figure 2 Gene editing process The principles of gene editing involve selecting target genes, designing guide RNA to direct Cas9, and utilizing the cell's repair mechanisms to achieve precise editing of target genes. This process provides a powerful tool for dairy cow improvement, with the potential to enhance milk production and quality, marking a revolutionary advancement in the agricultural sector. 2.3 Prospects of CRISPR-Cas9 technology in dairy cow improvement The prospects of CRISPR-Cas9 technology in dairy cow improvement have garnered widespread attention as it offers a new pathway for enhancing milk production and quality in dairy cow. CRISPR-Cas9 technology can be employed to boost the lipid synthesis capacity of dairy cow, directly impacting the fat content of dairy products. By editing genes associated with lipid synthesis, researchers can regulate the production and accumulation of fatty acids, thus increasing the fat content in milk. Through precise editing of key genes in the lipid synthesis pathway, scientists can achieve not only an increase in fat content but also adjust the fatty acid composition to produce healthier fats, such as dairy products rich in unsaturated fatty acids. With the global population continually increasing and the dairy market expanding, the urgent need to enhance dairy production has become paramount in the agricultural sector. CRISPR-Cas9 technology provides new possibilities for achieving this goal. By editing genes related to both lipid synthesis and milk protein synthesis, scientists can improve the milk-producing performance of dairy cow. This includes not only increasing the daily milk yield per cow but also enhancing the protein content in dairy products. Improving the composition of milk proteins allows for the production of more diverse dairy products, such as high-protein yogurt, shakes, and dairy ingredients. Increasing dairy production in cow can reduce adverse environmental impacts. By enhancing the milk production of individual cows, it becomes possible to achieve the same amount of dairy output with fewer cows. This reduces the resource demands of the dairy industry, including feed, water, and land, thereby alleviating the pressure on greenhouse gas emissions and land use. Improving the health and resilience of dairy cow reduces reliance on antibiotics and medications, contributing to a reduction in the risk of drug residues in dairy products. Gene editing can lower the risk of potential pathogenic microorganisms and harmful substances in dairy products, thus enhancing food safety. Scientists can increase the efficiency of the immune system by editing genes in dairy cow, reducing the chances of cows contracting diseases and, consequently, lowering the potential risk of pathogens entering dairy products. Editing genes in dairy cow to decrease the levels of specific harmful
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