Microbiology and Immunology

(Axel Boer) #1
AIDS WORLD OF MICROBIOLOGY AND IMMUNOLOGY

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ery, a dispute ensued over who made the initial discovery, but
today Gallo and Montagnier are credited as co-discoverers.
Inside its host cell, the HIV retrovirus uses an enzyme
called reverse transcriptase to make a DNA copy of its genetic
material. The single strand of DNA then replicates and, in dou-
ble stranded form, integrates into the chromosome of the host
cell where it directs synthesis of more viral RNA. The viral
RNA in turn directs the synthesis protein capsids and both are
assembled into HIV viruses. A large number of viruses emerge
from the host cell before it dies. HIV destroys the immune sys-
tem by invading lymphocytes and macrophages, replicating
within them, killing them, and spreading to others.
Scientists believe that HIV originated in the region of
sub-Saharan Africa and subsequently spread to Europe and the
United States by way of the Caribbean. Because viruses exist
that suppress the immune system in monkeys, scientists
hypothesize that these viruses mutated to HIV in the bodies of
humans who ate the meat of monkeys, and subsequently
caused AIDS. A fifteen-year-old male with skin lesions who
died in 1969 is the first documented case of AIDS. Unable to
determine the cause of death at the time, doctors froze some of
his tissues, and upon recent examination, the tissue was found
to be infected with HIV. During the 1960s, doctors often listed
leukemia as the cause of death in many AIDS patients. After
several decades however, the incidence of AIDS was suffi-
ciently widespread to recognize it as a specific disease.
Epidemiologists, scientists who study the incidence, cause,
and distribution of diseases, turned their attention to AIDS.
American scientist James Curran, working with the Centers
for Disease Controland Prevention (CDC), sparked an effort
to track the occurrence of HIV. First spread in the United
States through the homosexual community by male-to-male
contact, HIV rapidly expanded through all populations.
Presently new HIV infections are increasing more rapidly
among heterosexuals, with women accounting for approxi-
mately twenty percent of the AIDS cases. The worldwide
AIDS epidemic is estimated to have killed more than 6.5 mil-
lion people, and infected another 29 million. A new infection
occurs about every fifteen seconds. HIV is not distributed
equally throughout the world; most afflicted people live in
developing countries. Africa has the largest number of cases,
but the fastest rate of new infections is occurring in Southeast
Asia and the Indian subcontinent. In the United States, though
the disease was concentrated in large cities, it has spread to
towns and rural areas. Once the leading cause of death among
people between the ages of 25 and 44 in the Unites States,
AIDS is now second to accidents.
HIV is transmitted in bodily fluids. Its main means of
transmission from an infected person is through sexual con-
tact, specifically vaginal and anal intercourse, and oral to gen-
ital contact. Intravenous drug users who share needles are at
high risk of contracting AIDS. An infected mother has a 15 to
25% chance of passing HIV to her unborn child before and
during birth, and an increased risk of transmitting HIV
through breast-feeding. Although rare in countries such as the
United States where blood is screened for HIV, the virus can
be transmitted by transfusions of infected blood or blood-clot-
ting factors. Another consideration regarding HIV transmis-

sion is that a person who has had another sexually transmitted
disease is more likely to contract AIDS.
Laboratories use a test for HIV-1 that is called Enzyme-
linked immunosorbant assay (ELISA). (There is another type of
HIV called HIV-2.) First developed in 1985 by Robert Gallo
and his research team, the ELISA test is based on the fact that,
even though the disease attacks the immune system, B cells
begin to produce antibodies to fight the invasion within weeks
or months of the infection. The test detects the presence of
HIV-1 type antibodies and reacts with a color change.
Weaknesses of the test include its inability to detect 1) patients
who are infectious but have not yet produced HIV-1 antibodies,
and 2) those who are infected with HIV-2. In addition, ELISA
may give a false positive result to persons suffering from a dis-
ease other than AIDS. Patients that test positive with ELISA are
given a second more specialized test to confirm the presence of
AIDS. Developed in 1996, this test detects HIV antigens, pro-
teins produced by the virus, and can therefore identify HIV
before the patient’s body produces antibodies. In addition, sep-
arate tests for HIV-1 and HIV-2 have been developed.
After HIV invades the body, the disease passes through
different phases, culminating in AIDS. During the earliest
phase the infected individual may experience general flu-like
symptoms such as fever and headache within one to three
weeks after exposure; then he or she remains relatively
healthy while the virus replicates and the immune system pro-
duces antibodies. This stage continues for as long as the
body’s immune response keeps HIV in check. Progression of
the disease is monitored by the declining number of particular
antibodies called CD4-T lymphocytes. HIV attacks these
immune cells by attaching to their CD4 receptor site. The
virus also attacks macrophages, the cells that pass the antigen
to helper T lymphocytes. The progress of HIV can also be
determined by the amount of HIV in the patient’s blood. After
several months to several years, the disease progresses to the
next stage in which the CD4-T cell count declines, and non-
life-threatening symptoms such as weakness or swollen lymph
glands may appear. The CDC has established a definition for
the diagnosis of AIDS in which the CD4 T-cell count is below
200 cells per cubic mm of blood, or an opportunistic disease
has set in.
Although progress has been made in the treatment of
AIDS, a cure has yet to be found. In 1995 scientists developed
a potent cocktail of drugs that help stop the progress of HIV.
Among other substances, the cocktail combines zidovudine
(AZT), didanosine (ddi), and a protease inhibitor. AZT and ddi
are nucleosides that are building blocks of DNA. The enzyme,
reverse transcriptase, mistakenly incorporates the drugs into
the viral chain, thereby stopping DNA synthesis. Used alone,
AZT works temporarily until HIV develops immunity to the
nucleoside. Proteases are enzymesthat are needed by HIV to
reproduce, and when protease inhibitors are administered,
HIV replicates are no longer able to infect cells. In 1995 the
Federal Drug Administration approved saquinaviras, the first
protease inhibitor to be used in combination with nucleoside
drugs such as AZT; this was followed in 1996 by approval for
the protease inhibitors ritonavir and indinavir to be used alone
or in combination with nucleosides. The combination of drugs

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