progression to Acquired
Immunodeficiency
Syndrome (AIDS). For
example, a 32 base-pair
deletion in CCR5 (see
Figure 1) protects the host
from being infected even if
exposed to HIV-1. Among
European Caucasians, the
proportion of individuals
each with two copies of
the deletion is only about
0.1%. Even those with
one copy of the deletion
get some protection in
terms of lower viral load;
the proportion of such
individuals is about 17%.
In India, the deletion
allele is absent in most
ethnic groups (Majumder
PP and Dey B: European
Jour Hum Genet 9: 794;
2001), Chemokines
are natural ligands for
receptors that HIV-1 uses
to enter the cells; these
chemokine s compete with
the virus for co-receptor
binding and influence
susceptibility to HIV-1.
Several polymorphisms
located in (1) regulatory
regions of CCL5 (encoding
CC-chemokine RANTES),
and (2) coding and non-
coding regions of MIP1α
have been associated with
both resistance to HIV-1
infection and progression.
Polymorphisms resulting
in increased expression
of chemokines notably
reduce the risk of
acquiring HIV-1.
Even though, numerous
host factors that support
HIV-1 replication have
been identified using
large scale siRNA (small
interfering RNA) screens,
genetic variants of only
tumor susceptibility gene
101 (TSG101: -183T>C
and +181A>C) and
peptidyl propyl isomerase
A (PPLA) genes were
confirmed to modulate
HIV pathogenesis. In
parallel to expression
of HIV-1 supporting
factors, human genome
encodes molecules that
are intrinsic inhibitors
of HIV-1 replication:
most notably TRIM5α
and APOBEC3G. Of
these, common variants
of TRIM5α suggest that
it has no or only modest
influence on HIV-1
disease outcome. An
H186R coding change in
APOBEC3G is reported
to be associated with
accelerated progression
to AIDS in African
population; thorough
analysis in Caucasians did
not show any association
with HIV-1 control.
Human genes critical
to immunity or
inflammation also play
role in HIV-1 pathogenesis
and have been of interest
for genetic studies.
Polymorphisms in the
genes encoding cytokines,
cytokine receptors have
been associated with both
resistance and disease
progression. In this
regard, variants in genes
responsible for innate
immunity to HIV-1 such
as: (i) β-defensin 1 gene
(DEFB1) are associated
with higher level of
HIV-1 RNA in breast
milk, and (ii) mannose-
binding lectin 2 protein
(encoded by MBL2) with
increased susceptibility
to HIV-1 infection
and/or accelerated
disease progression, iii)
polymorphisms in TLR-7
and -9 influence disease
progression.
Since the identification
of CCR5-^32, an allele
of CCR5 with a 32 bp
deletion responsible for
resistance to R5-virus
acquisition, human
genetics has undergone
massive transitions
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