364
U N I T 4
Infection and Immunity
T cells, the proviral cDNA may remain in the cytoplasm
in a linear extrachromosomal form. The
fifth step
involves
transcription
of the double-stranded viral DNA
to form a single-stranded messenger RNA (mRNA) with
the instructions for building new viruses. Transcription
involves activation of the T cell and induction of host
cell transcription factors. Alternatively, the provirus
may remain nontranscribed within infected cells for
months or years, hidden from the host’s immune system
and even from antiviral therapies. Long-lived reservoirs
of HIV are established within the first month of acute
infection.
46
These reservoirs of latent infected cells do
not spontaneously produce virus unless activated. Their
long life span constitutes one of the main barriers to
HIV eradication by current antiviral therapies.
The
sixth step
includes translation of the viral mRNA.
During
translation,
ribosomal RNA (rRNA) uses the
instructions in the mRNA to create a chain of proteins
and enzymes called a
polyprotein.
These polyproteins
contain the components needed for the next stages in the
construction of new viruses. The
seventh step
is called
cleavage.
During cleavage, the protease enzyme cuts the
polyprotein chain into the individual proteins that will
make up the new viruses. Finally, during the
eighth step,
the core proteins migrate to the cell membrane, where
they acquire a lipid envelope that buds off from the cell
membrane. Productive infections, associated with exten-
sive viral budding, lead to cell death.
2
It is important
to note that although HIV can infect resting cells, the
initiation of transcription and viral replication occurs
only when the infected cell is activated by exposure to
antigens or cytokines.
Within 72 hours of a transmission event, local virus
replication occurs at the site of infection and the draining
lymph nodes.
46
Infection becomes systemic by the end of
the first week, as the virus disseminates to other lym-
phoid tissue compartments. By day 10 after infection,
most circulating CD4
+
T cells either have been infected
with or have interacted with HIV. The availability and
rapid consumption of targets during this early period
leads to massive viral replication, accounting in part for
the high levels of viremia and genital shedding achieved
by the end of the first month. Once infection has become
truly systemic, viral loads grow exponentially, with a
FIGURE 16-8.
(A)
Structure of the human immunodeficiency virus (HIV). RNA, ribonucleic acid.
(B)
Life cycle of HIV-1. (1) Attachment of the HIV virus to CD4
+
T-cell receptor; (2) internalization and
uncoating of the virus with viral RNA and reverse transcriptase; (3) reverse transcription, which
produces a mirror image of the viral RNA and double-stranded DNA molecule; (4) integration of viral
DNA into host DNA using the integrase enzyme; (5) transcription of the inserted viral DNA to produce
viral messenger RNA; (6) translation of viral messenger RNA to create viral polyprotein; (7) cleavage
of viral polyprotein into individual viral proteins that make up the new virus; and (8) assembly and
release of the new virus from the host cell.
Lipid
membrane
Reverse
transcriptase
RNA
gp
120
gp
41
p
17
matrix
p
24
capsid
Integrase
Protease
A
gp120
1
2
3
4
5
6
7
8
CD4
+
binding site
Reverse
transcriptase
Viral
polyprotein
B
