Biology Reference
In-Depth Information
can also cause AIDS, and is especially endemic to Western Africa, but is less
pathogenic than HIV-1. The following comments relate primarily to HIV-1.
The infectious HIV-1 particle (virion) is a spherical/icosahedral structure.
The outer coat (envelope) is a lipid bilayer primarily derived from the host cell
membrane and spiked with the speci®c HIV-1 glycoproteins, gp120 and gp41.
Contained within the spherical structure is the cone-shaped nucleocapsid,
composed of the major core protein HIV p24. Within the nucleocapsid struc-
ture, the retroviral capsid contains two identical copies of HIV-1 RNA, and
several critical enzymes, including reverse transcriptase ( RT ), integrase, and
protease. Each single-stranded RNA is 9.2-kb long and rich in adenosine de-
oxyribonucleotide residues, distinct from host cell genes (Kypr et al., 1989).
The two identical viral RNA copies are composed of both structural (e.g., gag,
pol, and env) and regulatory genes (e.g., tat, rev). The structural genes include
env, which is the precursor for the envelope glycoprotein (gp120 and gp41); gag,
which is the precursor for the virion core proteins (including p24); and pol,
which is the precursor for virion enzymes including reverse transcriptase, pro-
tease and integrase. The genes can be further characterized as essential, or re-
quired for viral replication (e.g., gag, pol, env, tat, and rev), and nonessential
accessory or auxilliary genes (e.g., vpr, vif, vpu,andnef ).
HIV-1 can infect a variety of cells expressing the appropriate surface re-
ceptors. In general, HIV-1 infects susceptible cells by interaction of the gp120
glycoprotein with receptors on the surface of host cells, namely CD4 and
chemokine receptors. In general, monocytotropic isolates of HIV-1 utilize the
CCR5 chemokine receptor along with the CD4 receptor, whereas lymphocyto-
tropic HIV-1 isolates utilize CXCR4 chemokine receptor in association with
the CD4 receptor. The cell tropism of HIV-1 is determined primarily by the
speci®c amino acid residues located in the 35-amino acid V3 (loop) variable
domain sequence of the gp120 molecule. In general, the initial infection with
HIV-1 of susceptible subjects involves a monocytotropic isolate of HIV-1 (M-
tropic or C5), whereas HIV-1 disease progression is associated with evolution
of the virus to acquire more lymphocytotropic characteristics (T-tropic or
CX4).
Receptor-mediated entry is the major pathway for HIV-1 infection of sus-
ceptible cells. HIV-1 gp120 binds to the CD4 receptor on the host cell surface,
inducing a conformational change in the gp120 molecule, which exposes the
hydrophobic fusion peptide, gp41. HIV-1 gp41 then inserts its fusion domain
into the host cell membrane, bringing together the host membrane and the
viral envelope, which promotes membrane fusion and the release of the HIV-1
nucleocapsid into the cell cytoplasm.
As the HIV-1 nucleocapsid enters the host cell, it is uncoated, and each HIV-
1 RNA is reverse transcribed to yield a double-stranded DNA replica of the
original RNA genome, although now containing tandem long-terminal re-
peat ( LTR) regions rather than the native short-terminal repeat regions of the
native HIV-1 RNA. The newly synthesized HIV-1 DNA is transported into the
