AIDS/HIV, Molecular and Cell Biology
103
Env (SU/gp120)
Env (TM/gp41)
MA (p17)
CA (p24)
Dimeric
RNA genome
coated by NC (p7)
Membrane
p6
PR
RT
IN
Vpr/x
Vif
Nef
Fig. 3
Diagram of HIV 1 virus particle.
Within the mature virus particle, the inner
surface of the envelope is lined by the
matrix protein (MA), a cleavage deriva-
tive of the major core polyprotein, Gag.
Within this is a pyramidal core structure
made up of capsid (CA) protein subunits.
This encloses the two copies of the RNA
genome that are coated with the nucleocap-
sid (NC) protein. The two RNAs are tightly
linked at a site known as the
dimer linkage
site
(DLS). Each has a cell-derived tRNA
lys
annealed to a complementary sequence
at the 5
0
end of the genome, the primer
binding site. Within the particle are a num-
ber of viral accessory proteins including
Vif and Vpr. The virus also captures a
number of cellular proteins including gly-
coproteins from the plasma membrane of
the cell in its envelope and a number of
cytoplasmic proteins including cyclophilin
that binds speciFcally to the capsid pro-
tein in the core. The viral gene products
of the
pol
gene are also incorporated into
the virus. These include the protease (Pro)
that cleaves the Gag and Pol precursor
polyproteins to generate Gag products (p6,
p7, p17, and p24) and Pol products in-
cluding the reverse transcriptase enzyme
(RT), which is responsible for generating a
DNA copy from the RNA genome and the
integrase enzyme (IN) that inserts the viral
DNA into the chromosomes of the target
cell.
2.2
Life cycle
Infection of a cell by HIV occurs following
binding of the virus through its SU
glycoproteins to the cell surface molecule
CD4 and coreceptors (±ig. 4). The CD4
glycoprotein is found on a variety of cells,
predominantly in those of the immune
system. HIV tropism is broadly divided
into viruses that can infect T lymphocytes
(T-cell tropic) and those that infect cells
of the macrophage/monocyte lineage (M
tropic) (see Sect. 2.4).
Binding to the cell is followed by a con-
formational change in TM in which its
hydrophobic terminus penetrates the tar-
get cell membrane and approximates it to
the viral envelope lipids, fusing the two
membranes together. Cellular lipid rafts
appear to play a role in virus entry. The
capsid and its contents enter the cell cy-
toplasm and the processes of disassembly
and reverse transcription begin in which
the viral RNA is copied into a DNA form.
Reverse transcription is shown in ±ig. 5.
More detailed accounts can be found in the
literature. Two important features of the
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