HIV and its lifecycle

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HIV and its lifecycle Sources Wikipedia,
http//www.bio.davidson.edu/courses/HIVcellsalive
HIV is a retrovirus (enveloped viruses possessing
an RNA genome, and replicate via a DNA
intermediate), that can lead to AIDS.
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Attachment to Lymphocyte membrane
Entry of the viral RNA
HIV sticks to (at least) two receptors on the
T-lymphocytes. The primary receptor, called
"CD4", is shown on the right in the diagram. But
a second receptor that loops through the cell
membrane 7 times is critical for infection to
occur. HIV infection of a lymphocyte requires
attachment of the virus to the cell membrane
through both of these "ligand-receptor" links.
Tight attachment of the viral particle to
receptors on the lymphocyte membrane enables
fusion with the cell membrane. The viral
contents, including viral RNA (shown in yellow)
then empty into the cell's cytoplasm.
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Replication
Integration, transcription
HIV RNA
Host cell DNA
Reverse Transcriptase
Viral DNA
The virus has its own enzyme called "integrase"
that facilitates incorporation of the viral DNA
into the host cells DNA.
Complementary DNA
Reverse transcriptase, a enzyme that's part of
HIV, reads the sequence of viral RNA nucleic
acids that have entered the host cell and
transcribes the sequence into a complementary DNA
sequence. Reverse transcriptase sometimes makes
mistakes, leading to point mutations in the RNA
and hence different HIV surface proteins, so that
HIV cant be recognized by existing antibodies
anymore.
T-cells RNA polymerase
viral mRNA
If the lymphocyte is activated, transcription of
the viral DNA begins, resulting in the production
of multiple copies of viral RNA.
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Viral protease
Translation
Before these enzymes become functional, they must
be cut from the longer polypeptide chain. Viral
protease cleaves the long chain into its
individual enzyme components which then
facilitate the production of new viruses.
There are only 9 genes in the HIV RNA. Those
genes have the code necessary to produce
structural proteins such as the viral envelope
and core plus enzymes like reverse transcriptase,
integrase, and a crucial enzyme called a
protease. When viral RNA is translated into a
polypeptide sequence, that sequence is assembled
in a long chain that includes several individual
proteins (reverse transcriptase, protease,
integrase)..
Protease inhibitors (e.g. ritonavir) block the
ability of the protease to cleave, so the new
virus wont have its functional enzymes and wont
be able to reproduce.
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Assembly and Budding

• Finally, viral RNA and associated proteins are
  packaged and released from the lymphocyte
  surface, taking with them a swatch of lymphocyte
  membrane containing viral surface proteins. These
  proteins will then bind to the receptors on other
  immune cells facilitating continued infection.
• Budding viruses are often exactly like the
  original particle that initially infected the
  host. In the case of HIV, however, the resulting
  viruses exhibit a range of variations which makes
  treatment difficult.

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HIV-1 Dynamics in Vivo
HIV-1 infects T-lymphocytes with a rate k,
infection turns the T-cells into productively
infected cells (T) each of which produces about
N new viruses on average. If the cell contains
ritonavir it will produce only non-infectious
viruses. The release of viruses usually causes
the cell to die. A cell dies with likelihood of d
(per cell, i.e. percentage). No infectious
viruses are produced. On average N non-infectious
viruses from a (dying) cell are produced.
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Initial conditions and further assumptions
blackboard