Biomedical Engineering Reference
In-Depth Information
Infection of CD4
cells commences via interaction between gp 120 and the CD4 glycoprotein,
which effectively acts as the viral receptor. Entry of the virus into the cell, which appears to re-
quire some additional cellular components, occurs via endocytosis and/or fusion of the viral and
cellular membranes. The gp 41 transmembrane protein plays an essential role in this process.
Once released into the cell, the viral RNA is transcribed (by the associated viral reverse tran-
scriptase) into double-stranded DNA. The retroviral DNA can then integrate into the host cell genome
(or, in some instances, remain unintegrated). In resting cells, transcription of viral genes usually
does not occur to any signifi cant extent. However, commencement of active cellular growth /differen-
tiation usually also triggers expression of proviral genes and, hence, synthesis of new viral particles.
Aggressive expression of viral genes usually leads to cell death. Some cells, however (particularly
macrophages), often permit chronic low-level viral synthesis and release without cell death.
Entry of the virus into the human subject is generally accompanied by initial viral replication,
lasting a few weeks. High-level viraemia (presence of viral particles in the blood) is noted and p24
antigen can be detected in the blood. Clinical symptoms associated with the initial infection include
an infl uenza-like illness, joint pains and general enlargement of the lymph nodes. This primary
viraemia is brought under control within 3-4 weeks. This appears to be mediated largely by HIV-
specifi c cytotoxic T-lymphocytes, indicating the likely importance of cell-mediated immunity in
bringing the initial infection under control. Although HIV-specifi c antibodies are also produced at
this stage, effective neutralizing antibodies are detected mainly after this initial stage of infection.
After this initial phase of infection subsides, the free viral load in the blood declines, often to
almost undetectable levels. This latent phase may last for anything up to 10 years or more. During
this phase, however, there does seem to be continuous synthesis and destruction of viral parti-
cles. This is accompanied by a high turnover rate of (CD4
) T-helper lymphocytes. The levels
of these T-lymphocytes decline with time, as does antibody levels specifi c for viral proteins. The
circulating viral load often increases as a result, and the depletion of T-helper cells compromises
general immune function. As the immune system fails, classical symptoms of AIDS-related com-
plex (ARC) and, fi nally, full-blown AIDS begin to develop.
In excess of 40 million individuals are now thought to be infected by HIV. In 2001 alone, it was
estimated that 3 million people died from AIDS and a further 5 million became infected with the
virus. Over 20 million people in total are now thought to have died from AIDS. The worst affected
geographical region is the southern half of Africa (Table 13.11). Some 90 per cent of sufferers live
in poorer world regions. So far, no effective therapy has been discovered, and the main hope of
eradicating this disease lies with the development of safe, effective vaccines. The fi rst such puta-
tive vaccine entered clinical trials in 1987; but, thus far, no effective vaccine has been developed.
Table 13.11
WHO estimated numbers of individuals infected with HIV by the
end of 2005. Almost 75 per cent of these live in the southern half of Africa
World region
Numbers infected
Sub-Saharan Africa
25.8 million
South and South East Asia
7.4 million
Latin America
1.8 million
North America
1.2 million
Eastern Europe and central Asia
1.6 million
North Africa and Middle East
0.51 million
Western and central Europe
0.72 million
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