Transcript HIV - Penn Math

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.
Attachment to Lymphocyte membrane
HIV sticks to (at least) two receptors on the Tlymphocytes.
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.
Entry of the viral RNA
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.
Replication
Integration, transcription
HIV RNA
Reverse Transcriptase
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 can’t be recognized by existing antibodies
anymore.
Host cell DNA
Viral DNA
The virus has its own enzyme called
"integrase" that facilitates incorporation
of the viral DNA into the host cells DNA.
T-cell’s RNA
viral mRNA polymerase
If the lymphocyte is activated,
transcription of the viral DNA
begins, resulting in the
production of multiple copies of
viral RNA.
Translation
Viral protease
Protease
Protein
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)..
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.
Protease inhibitors (e.g.
ritonavir) block the
ability of the protease to
cleave, so the new virus
won’t have its functional
enzymes and won’t be
able to reproduce.
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.
HIV-1 Dynamics in Vivo
InfectiousVirion
Replication N copies on
average
T-cell + ritonavir
Non-infectious Virion
STOP
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 δ (per
cell, i.e. percentage). No infectious viruses are produced. On average N noninfectious viruses from a (dying) cell are produced.
Initial conditions and further assumptions
blackboard