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come together, infection does not take place. Millions of HIV tainted cells can be
launched from a single infected cell. This technique can be used in the ongoing
studies of the effects of drugs in the process of assembly and disassembly of the
viral DNA integrase complexes.
The genome of HIV contains three major genes − gag, pol − and env, which code
for the major structural and functional components of HIV, including envelope pro-
teins and reverse transcriptase. The major structural components coded by env
include the envelope glycoproteins, including the outer envelope glycoprotein
gp120 and transmembrane glycoprotein gp41 derived from glycoprotein precursor
gp160. Major components coded by the gag gene include core nucleocapsid pro-
teins p55, p40, p24 (capsid, or “core” antigen), p17 (matrix), and p7 (nucleocapsid);
the important proteins coded by pol are the enzyme proteins p66 and p51 (reverse
transcriptase), p11 (protease), and p32 (integrase). Elucidating the genes infl uenc-
ing risk of HIV-1 infection and disease progression may help target areas for inter-
vention, such as vaccine development.
The pathogenesis of HIV infection is a function of the virus life cycle, host cel-
lular environment, and quantity of viruses in the infected individual. After entering
the body, the viral particle is attracted to a cell with the appropriate CD4 receptor
molecules where it attaches by fusion to a susceptible cell membrane or by endocy-
tosis and then enters the cell. The probability of infection is a function of both the
number of infective HIV virions in the body fl uid which contacts the host as well as
the number of cells available at the site of contact that have appropriate CD4
receptor.
Immune activation is a hallmark of HIV infection and a signifi cant factor in con-
tinuous viral replication and CD4+ T cell depletion. In HIV-infected individuals,
levels of circulating activation markers correlate with accelerated disease progres-
sion and shortened survival. HIV infection is critically dependent on the activated
state of CD4+ T cells since quiescent T cells in blood are refractory to HIV infec-
tion. In addition, T-cell activation enhances viral transcription through activation of
transcription factors, such as nuclear factor kB. HIV infection itself manipulates the
activation status of infected T cells through the expression of viral proteins includ-
ing the viral transactivator Tat, which potently activates HIV transcription. Tat also
infl uences the expression of cellular genes in infected T cells. While the function of
Tat in viral transcription is well studied, the molecular mechanism underlying its
immunomodulatory effects is less clear.
The asymptomatic phase of HIV infection is characterized by a slow decline of
peripheral blood CD4+ T cells. One potential explanation of why this decline is
slow is that the low average rate of immune activation dictates the pace of a “run-
away” decline of memory CD4+ T cells, in which activation drives infection, higher
viral loads, increased recruitment of cells into an activated state, and further infec-
tion events. Some alternative mechanisms include the phenomenon of viral rebound,
in which interruption of antiretroviral therapy causes a rapid return to pretreatment
viral load and T cell counts, supporting the role of virus adaptation as a major force
driving depletion.
11 Personalized Management of Infectious Diseases