Page 8 - AIDSBK23C

Page 8

BIOLOGY OF HUMAN IMMUNODEFICIENCY VIRUS

Human immunodeficiency virus (HIV) and its subtypes are retroviruses, and they are the
etiologic agents of AIDS. Human retroviruses were unknown until the 1980's, though animal
retroviruses such as feline leukemia virus had been detected previously. HIV belongs to a large
family of ribonucleic acid (RNA) lentiviruses that are characterized by association with diseases
of immunosuppression or central nervous system involvement and with long incubation periods
following infection before manifestations of illness become apparent.[21,22]
Lentiviruses similar to HIV have been found in a variety of primate species, and some of
these are associated with a disease process called simian AIDS. Unlike other retroviruses, the
primate lentiviruses are not transmitted through the germ line, and no endogenous copies of the
virus exist in the genome of susceptible species.[23] Molecular epidemiologic data suggest that
HIV type 1, the most common subtype of HIV that infects humans, has been derived from the
simian immunodeficiency virus, called SIVcpz, of the Pan troglodytes troglodytes subspecies of
chimpanzee. The lentivirus strain SIVcpz is highly homologous with HIV-1, and another form
of simian immunodeficiency virus found in sooty mangabeys (SIVsm) has similarities as well
and likely gave rise to HIV-2. There is molecular epidemiologic evidence for multiple cross-
th
species transmissions of SIV to humans occurring in the first half of the 20 century, probably
through exposures to primate blood.[24]
th
Zoonotic infection of humans may have occurred long in the past, but only in the late 20
century did demographic and social conditions change significantly to permit HIV to spread
more rapidly. Zoonotic infection of man with retroviruses is possible, as documented by
infection of primate handlers with simian foamy retroviruses.[25] Retrospective studies
performed on frozen sera have shown evidence for HIV in patients in Africa prior to 1960.[26]
Reports in the early 1980's referred to the agent causing AIDS as either human T-
lymphocytotropic virus, type III (HTLV-III) or as lymphadenopathy associated virus (LAV).
This originally discovered virus is known as HIV-1, with one additional major subtype
discovered, called HIV-2, which has more similarity to simian immunodeficiency virus (SIV)
than to HIV-1.[27,28]
The mature virus consists of a bar-shaped electron dense core containing the viral
genome--two short strands of ribonucleic acid (RNA) about 9200 nucleotide bases long--along
with the enzymes reverse transcriptase, protease, ribonuclease, and integrase, all encased in an
outer lipid envelope derived from a host cell. This envelope has 72 surface projections, or
spikes, containing an antigen, gp120 that aids in the binding of the virus to the target cells with
CD4 receptors. A second glycoprotein, gp41, binds gp120 to the lipid envelope.[22,29,30]
By electron microscopy, the plasma membrane of an infected CD4+ lymphocyte exhibits
budding virus particles approximately 100 nanometers in diameter. The virion has an
asymmetric core consisting of a conical capsid (a geometric “fullerine cone”) with a broad
electron dense base and hollow tapered end. Virions bud from plasma membranes or from
cytoplasmic vacuoles of infected host cells. Spikes are inserted onto the membrane of the
developing virion, which buds to a complete sphere. Aberrant virion formation is common,
including double buds, giant virions, empty nucleoids, and misplaced electron dense material.
Simplistic organisms such as lentiviruses just do not have the error checking genetic equipment
for quality assurance, but make up for it with sheer numbers of particles released.[30,31]