the San Francisco V.A. Medical Center have discovered a
possible answer to a long-standing AIDS mystery--why
only some HIV-positive people go on to develop
HIV-related dementia. Their study of 18 HIV-positive
subjects shows that HIV in the brain and central nervous
system is genetically different from HIV in the blood and
peripheral tissues. Serious cognitive impairment among
the study subjects was correlated with the presence of
a particular mutation in the HIV envelope gene in
virus detected in the brain and nervous system.
generated 456 nucleotide sequences of HIV from the blood
and cerebrospinal fluid of the study participants. They
chose to focus on the viral envelope gene, which
interacts with receptors on
the surfaces of
host cells. "That's the gene that's most likely to vary
between tissues, because it evolves rapidly and allows
the virus to dock with different cell types," said
lead researcher Satish K. Pillai in a press
Pillai, an analysis of the sequence data suggests that HIV
is "genetically compartmentalized" between the central
nervous system and the blood, "which means that the
virus is replicating in relative isolation in these
tissues, with very little exchange of genetic
information between the two populations."
also analyzed the sequences in search of a "genetic
signature" common to the central nervous
system-specific viruses in all 18 individuals.
They found such a pattern, consisting of four
acids, within a subregion of the viral envelope
gene known as the V3 loop. Another mutation in
the V3 loop appeared consistently in virus from study
subjects who demonstrated the most severe cognitive
impairment. This mutation was absent in sequences from
subjects with little or no cognitive problems.
"In other words,"
said Pillai in the press statement, "there appears to
be a particular HIV mutation that is associated with
Identifying the genetic variant in HIV
patients could help predict whether they are at risk
for developing HIV-related dementia, added Pillai.
This could help doctors prescribe antiretroviral drugs with
a better ability to cross the blood-brain barrier to inhibit
viral replication in the brain and central nervous
system, Pillai said.
The study appears
in the July 2006 issue of the journal Brain. (The