| Life Cycle of HIV Infection
HIV begins its infection of a susceptible host cell by
binding to the CD4 receptor on the host cell. CD4 is present
on the surface of many lymphocytes, which are a critical
part of the body's immune system. Recent evidence indicates
that a coreceptor is needed for HIV to enter the cell. This
recognition of HIV coreceptors and progress in understanding
how HIV fuses with the cell has opened up new possibilities
for antiviral drugs. A number of new agents are being
designed to prevent infection by blocking fusion of HIV with
its host cell.
Following fusion of the virus with the host cell, HIV
enters the cell. The genetic material of the virus, which is
RNA, is released and undergoes reverse transcription into
DNA. An enzyme in HIV called reverse transcriptase is
necessary to catalyze this conversion of viral RNA into DNA.
Inhibitors of reverse transcriptase, such as AZT, were the
first anti-HIV medications, and are still a critical part of
treating patients who have HIV. Reverse transcriptase
inhibitors are divided into two classes-nucleoside analogues
and non-nucleoside reverse transcriptase inhibitors-based on
their structure and how they inhibit reverse transcriptase.
Once the genetic material of HIV has been changed into
DNA, this viral DNA enters the host cell nucleus where it
can be integrated into the genetic material of the cell. The
enzyme integrase catalyzes this process, and inhibitors of
integrase are under study as a new way to block HIV
replication. Once the viral DNA is integrated into the
genetic material of the host, it is possible that HIV may
persist in a latent state for many years. This ability of
HIV to persist in certain latently infected cells is the
major barrier to eradication or cure of HIV. For this
reason, based on our current knowledge, patients must remain
on anti-viral therapy for life.
Activation of the host cells results in the transcription
of viral DNA into messenger RNA (mRNA), which is then
translated into viral proteins. The new viral RNA forms the
genetic material of the next generation of viruses. The
viral RNA and viral proteins assemble at the cell membrane
into a new virus. Amongst the viral proteins is HIV
protease, which is required to process other HIV proteins
into their functional forms. Protease inhibitors, one of the
most potent types of anti-viral medications, act by blocking
this critical maturation step. Following assembly at the
cell surface, the virus then buds forth from the cell and is
released to infect another cell.
Unless the HIV lifecycle is interrupted by treatment, the
virus infection spreads throughout the body and results in
the destruction of the body's immune system. With current
anti-viral medications, such as reverse transcriptase
inhibitors and protease inhibitors, HIV infection can be
contained. However, a great deal more must be achieved
before AIDS epidemic is brought under control. One important
immediate goal is to design new, more potent medications
that are easier to take and have fewer side effects.
However, the ultimate challenges are to use our
understanding of the HIV lifecycle to develop medications
that will eradicate HIV from people who are already infected
and to create a vaccine that will prevent new infections in
the future.
Created by Rajesh Gandhi, M.D., John G. Bartlett,
M.D., Michael Linkinhoker, M.A., Medical Illustrator, May
1999. © 1999, Johns Hopkins University Division of
Infectious Diseases and AIDS Service.
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