Journal of Mosquito Research, 2013, Vol.3, No.1, 1-10
ISSN 1927-646X
http://jmr.sophiapublisher.com
6
(
Harapan et al., 2013). Abnormal expression of the
immune regulatory molecules, MICB, leads to
disturbances of regulatory T cell and NK immune
response (Jumnainsong et al., 2008) The MICB plays
a significant role in the immune response. The
mechanism of T cell and NK cell silencing by down
regulation of NKGD cells induced by soluble ligands
or chronic exposure to cell surface bound ligands may
represent an important mechanism in immune
responses (Jumnainsong et al., 2008; Marsh et al.,
2004).
Recently, one study by García et al (2011) in
Cuban populations, investigated the association of non
classical HLA class I MICA and MICB genes with
disease outcome during DENV infection. They found
that a tendency for MICA*008 and MICB*008 was
associate with susceptibility to DENV when
symptomatic versus asymptomatic cases were
compared. Garcia and group also found a stronger
association of both allelic forms was observed for the
dengue fever patients compared with the
asymptomatic dengue infection group rather than the
severe cases. This study concluded that the
polymorphisms of MICA and MICB gene contribute
to susceptibility against DENV infection in human.
2.4.2.
Lymphotoxin-alpha (LTA)
LTA are pleuripotent vasoactive immunomodulators
produced mainly by activated monocytes and
lymphocytes. LTA are encoded by adjacent gene loci
in the central or class
?
region of the human MHC
between HLA class I and
?
genes on the short-arm
of chromosome 6 (Horton et al., 2004). TNF and LTA
share the same receptors (Vejbaesya et al., 2009). LTA
promotes adhesion of molecules and cytokines from
EC and vascular smooth-muscle cells and play crucial
role in contributing to inflammatory cocktail (Ross,
1999).
This indicated that LTA plays crucial role in
DENV infection pathogenesis. A variety of SNPs have
been identified in non-coding promoter-like regions,
adjacent to exons encoding LTA (Fanning et al., 1997).
Furthermore, linkage disequilibrium between LTA,
and other HLA class I and
?
genes within the MHC
contributes to the formation of haplotypes or stable
combinations of SNP defined alleles, that vary in
composition and frequency both within and between
different ethnic groups (Baena et al., 2002;
Fanning et al.,1997; Shaw et al., 2004).
Several studies suggested that the polymorphisms in
the LTA gene may influence susceptibility to the
progression of chronic chagas cardiomyopathy
(
Ramasawmy et al., 2007) and coronary artery disease
and myocardial infarction (Knight et al., 2004; Tanaka
and Ozaki, 2006), heart failure (Ozaki et al., 2002),
asthma and other diseases (Knight et al., 2004).
An SNP identified within the LTA and TNF promoter
has been reportedly associated with DENV infection.
Vejbaesya et al (2009) analyzed several polymer-
phisms in TNF and LTA genes from patient with
subclinical DENV infection, primary and secondary
DF, and DHF in Thailand. They found that TNF-238A
marking the TNF-4, LTA-3 haplotype increased
significantly in secondary DHF patients compared to
secondary DF. They also found two that extended
MHC haplotypes containing TNF-4 and LTA-3,
together with HLA-B48, B57 and DPB1*0501, were
detected only in secondary DHF. This finding indicate
that polymorphism in functionally distinct MHC-
encoded proteins contributes to the risk of developing
severe secondary DENV infection and are worthy of
further investigation.
3.
Conclusion
In summary, we have shown that there are many
scientific evidences that have proven the fact
indicating host genetic factors as important
components in dengue disease. The roles of HLA and
HLA-related genes controlling DENV infection have
been proven by several scientific studies. HLA alleles
associated with DENV infection susceptibility,
severity and protection. In term of HLA-related
proteins, MICA, MICB and LTA also associated with
dengue manifestations. In suggestion, further analysis
of the genetic basis of DENV infection may contribute
to the development of new therapeutic and
preventative interventions.
Authors' Contributions
HH was the principal investigator, responsible for
work design, data collection and interpretation, drafted
the first and final manuscript, and revised the
manuscript. JKF and SAK participated in data