expert corner
Over the past
several years,
population studies
in HIV host genetics
have unraveled a
series of human
gene variants
that modulate
the response to
HIV exposure.
Genetic studies
have identified
genetic variants in
some chemokine
receptors CCR5,
CCR2, CX3CR1,
CXCR1 and CXCR6
that are associated
with HIV-1
acquisition and
progression to AIDS
and has provided new
insights in HIV-1 host
genetics. The Genome-
Wide Association Studies
(GWAS) performed in
populations of European
ancestry and African-
Americans have shown
that HLA class I variants
(notably HLA-B-*5701
and HLA-B-*5703,
respectively) are the
strongest determinants
of viral control. HLA
class I are fundamental
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BioVoiceNews | April 2017
in immune recognition
process and generating
cytotoxic T cell (CTL)
response; homozygosity
for class I alleles limits
diversity in epitope
recognition, impairing
anti-HIV CTL response
that leads to faster
progression and higher
viremia. In this regard,
HIV control is observed
to be better in individuals
with HLA-B*27, B*51 and
B*5801, but insufficient
in individuals with
HLA-B*5802 and alleles
from HLA-B35Px group.
Besides being key players
in CTL activity, HLA
class I molecules also
serve as ligands for killer
cell immunoglobulin-
like receptors (KIRs),
expressed on the surface
of natural killer (NK)
cells. KIRs regulate
activating or inhibitory
signals of NK cells thereby
directly modulate the
innate immune response
of HIV-1 infection. Certain
KIR genes and HLA class
I allele combinations,
particularly KIR3DL1 and
KIR3DS1 along with HLA-
Bw4 are associated with
better HIV-1 control and
delay disease progression.
Necessity to
improve precision
of transcriptome
analysis
It is intriguing that
besides the homozygosity
in CCR5-^32 decreasing
susceptibility to R5 HIV-
1 infection, other genetic
associations (CCR2-V64I,
SDF1-3’A, RANTES-403A-
28G or 28C, RANTES-
In1.1C, DC-SIGN-7/6
or 7/8, DC-SIGNR-7/5,
DC-SIGNR-7/7) are
biologically still poorly
understood. Surpassing
the information obtained
from genome wide
studies, novel approaches
including transcriptome
and proteome analysis
and siRNA screens
have been utilized
to understand the
modulation of prominent
anti-viral defense genes
in pathogenic versus
non-pathogenic infection
and NCBI HIV-1 Human
Protein Interaction
Database summarizes
over 3,000 protein
interactions with almost
1,500 human genes.
These still need to be
validated across the
disease spectrum and
various human ethnic
lineages. Of the 1,000
proteins identified using