110
AIDS/HIV, Molecular and Cell Biology
fact that the lymphocyte tropic viruses
have a surface envelope protein that pref-
erentially binds to the CXCR4 receptor
and the macrophage tropic to the CCR5
receptor. These tropisms are commonly
abbreviated by describing viruses as X4
or R5, respectively. More recently, a mu-
tation has been identiFed, which affects
about 1% of Caucasians who are ho-
mozygous for a stop codon causing a
truncation of the CCR5 protein, and ren-
ders these individuals uninfectable by
macrophage tropic virus. This explained
another observation that there were some
individuals who appeared to be repeat-
edly exposed to HIV through high-risk
sexual practices and yet did not become
infected.
3
Routes of Transmission
Infection can occur via cell-free virus or
through contact between infected cells and
those of the recipient. SIV in monkeys is
probably primarily transferred from host
to host by blood contact. HIV is also infec-
tious by blood contact but the predominant
mode of transmission is by the sexual
route. HIV positive mothers can trans-
mit the virus to their newborn child at
birth or through breast feeding. The fact
that cell-free virus is infectious means that
HIV was transmitted very efFciently in
clotting factor concentrates in the 1980s,
resulting in the infection of large cohorts
of hemophiliac patients. In the developed
world, blood donations are screened for
HIV as they are in many countries in the
developing world. There is a very small
but Fnite risk that a blood donor in the
‘‘window’’ period before seroconversion
may transmit an infection through blood
dona
t
ionbu
tth
i
si
sintheo
rde
ro
fle
s
s
than one in a million. Blood transmis-
sion occurs quite efFciently in the case
of intravenous drug users who share nee-
dles. Sexual transmission can occur from
both male to female and female to male
with an estimated risk of 1 : 200. Mucous
membrane transmission probably begins
with the infection of sessile cells of the
macrophage/monocyte system in the mu-
cous membrane tissues with subsequent
replication and spread of virus to other
cells of the immune system. Recent evi-
dence implicates Langerhans cells as the
Frst target. These may bind the virus us-
ing the DC-sign cell surface lectin, which
has a high afFnity for gp120. Whether
replication occurs within these cells or
whether surface-bound virus infects mi-
grating T cells and macrophages is not
established.
4
Natural History of Infection
The characteristic natural history of infec-
tion is illustrated in ±ig. 7. ±ollowing early
replication in lymph nodes and within
a period of approximately four to eight
weeks after exposure to virus, viremia be-
comes detectable in the form of ELISA
positivity to the p24 capsid antigen and
detection of viral RNA in the serum. This
viremia rises rapidly to a peak that may be
around Fve million copies of the viruses
per milliliter of blood. At this time, the be-
ginnings of an immune response against
the virus become detectable, including spe-
cial antibodies directed against the viral
proteins. Subsequently, the virus level in
the blood falls to a ‘‘set point’’ and this
correlates most closely with detection of
a rise in the cytotoxic T lymphocyte cell
mediated immunity. At the time of this
seroconversion, between a third and a
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