Journal of Mosquito Research, 2013, Vol.3, No.1, 1-10
ISSN 1927-646X
http://jmr.sophiapublisher.com
1
Research Report Open Access
Genetic Polymorphisms of HLA and HLA-Related Proteins: Implications on
Dengue Virus Infection
Harapan Harapan
1,2
,
Jonny K. Fajar
2
,
Said A. Khalilullah
2
,
Wira Winardi
2,3
,
Kurnia F. Jamil
1
1.
Tropical and Infection Diseases Division, Internal Medicine Department, School of Medicine Syiah Kuala University, Banda Aceh, Indonesia
2.
Medical Research Unit, School of Medicine Syiah Kuala University, Banda Aceh, Indonesia
3.
Graduate Institute of Medical Science, Taipei Medical University, Taipei, Taiwan
Corresponding author email:
harapantumangger@gmail.com
;
Authors
Journal of Mosquito Research, 2013, Vol.3, No.1 doi: 10.5376/jmr.2013.03.0001
Received: 28 Dec., 2012
Accepted: 10 Jan., 2013
Published: 15 Feb., 2013
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:
Harapan et al., 2013, Genetic Polymorphisms of HLA and HLA-Related Proteins: Implications on Dengue Virus Infection, Journal of Mosquito Research, Vol 3,
No.1 1-10 (doi: 10.5376/jmr.2013.03.0001)
Abstract
Dengue diseases pathogenesis is not yet completely understood. Several human immunities are controlled by the
expression of human leukocyte antigen (HLA) and expressions of HLA molecules are increased in dengue viral (DENV) infection.
The role of cytotoxic T lymphocyte recognizing DENV epitopes presented by the HLA is the basis for immunity of DENV infection.
The genes encoding HLA class I (HLA-A, -B, -C) and class
?
(
HLA-DR, DQ and DP) are the most polymorphic in the human
genome, and several specific polymorphisms in these genes influence peptide epitope binding. Here we have reviewed the
implication of HLA and HLA-related gene polymorphisms on DENV infection susceptibility, protection and severity. We found
several studies have identified HLA alleles associated with DENV infection susceptibility and severity such as A*0207, A*1, A*2,
A*24, A*31, B blank, B*13, B*40, B*46, B*51, B*52, B*53, B*57, DR1, DRB1*08, DRB1*12, DRB1*15 and TNF-a –308A allele.
Whereas some HLA alleles such as A*0203, A*03, A*29, A*33, B*13, B*14, B*15, B*18, B*44, B*49, B*52, B*62, B*76, B*77,
DRB1*0901, DRB1*02, DRB1*03, DRB1*04, and DRB1*07 are associated with DENV infection protection. In addition, HLA
class
?
and HLA-related proteins - mayor histocompatibility complex class I chain-related protein A and B (MICA and MICB) and
lymphotoxin-alpha (LTA) - also associated with DENV infection. In summary, HLA and several HLA-related proteins clearly play
important roles on DENV infection susceptibility, protection and severity.
Keywords
Dengue virus infection; DHF; DSS; SNP; Dengue disease severity; Polymorphism study; HLA
1.
Introduction
Dengue virus (DENV), a mosquito-borne flavivirus
infection of major international public health threat,
cause a spectrum of disease in humans, ranging from
dengue fever (DF), dengue hemorrhagic fever (DHF)
and dengue shock syndrome (DSS). It is estimated
that 50 million DENV infections occur annually
worldwide and it increased dramatically in recent
years (Guzman et al., 2010; WHO, 2009).
Approximately 2.5 billion people live in dengue
endemic countries and two fifths of the world's
population is at risk from DENV (WHO, 2006; 2009).
Vast majority of individuals infected with DENV
result in no symptoms and only about 2% develop
DHF, strongly suggesting the important role of host
genetic factors (Coffey et al., 2009). Halstead et al
(2001)
found that an absence of DHF in Haiti and
West Africa despite hyper endemic transmission of
multiple DENV serotypes. Furthermore, a study found
that blacks were less frequent develop to DHF/DSS
during DENV epidemics in Cuba (Coffey et al., 2009).
Although pre-existing immunity may be a
confounding factor in DENV infection development
but these studies reveal strong evident that genetic
predisposition is an important factor as well.
Development of DHF or DSS is not completely
understood. Progression of the dengue diseases is
different in each individual. It probably involves
several factors, such as immune response, antibody
dependent enhancement, virus virulence, and host
genetic (Panchal et al., 2012). Secondary viral
infection and host immunological factors are often