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The HIV replication cycle

Mechanism of Viral Entry/Membrane Fusion

1.Initial interaction between gp120 and CD4. 2.

Conformational change in gp120 allows for

secondary interaction with CCR5. 3.The distal tips

of gp41 are inserted in to the cellular membrane. 4.gp41 undergoes significant conformational change;

folding in half and forming coiled-coils. This

process pulls the viral and cellular membranes

together, fusing them.

membranes close together, allowing fusion of the membranes and subsequent entry of the viral capsid.[37][38]

After HIV has bound to the target cell, the HIV RNA and various enzymes, including reverse transcriptase,

integrase, ribonuclease, and protease, are injected into the cell.[37]During the microtubule-based transport to

the nucleus, the viral single-strand RNA genome is transcribed into double-strand DNA, which is then integrated

into a host chromosome.

HIV can infect dendritic cells (DCs) by this CD4-CCR5 route, but another route using mannose-specific C-type lectin receptors such as DC-SIGN can also be used.[40]DCs are one of the first cells encountered by the

virus during sexual transmission. They are currently thought to play an important role by transmitting HIV to T-

cells when the virus is captured in the mucosa by DCs. [40]The presence of FEZ-1, which occurs naturally in

neurons, is believed to prevent the infection of cells by HIV. [41]

Replication and transcription

Shortly after the viral capsid enters the cell, an enzyme called reverse transcriptaseliberates the single-

stranded (+)RNA genome from the attached viral proteins and copies it into a complementary DNA (cDNA)

molecule.[42]

The process

of reverse

transcription is

extremely

error-prone,

and the

resulting

mutations may

cause drugresistance or

allow the virus

to evade the

body's

immune

system. The

reverse transcriptase also has ribonuclease activity that degrades the

viral RNA during the synthesis of cDNA, as well as DNA-dependent

DNA polymerase activity that creates a sense DNA from the

antisensecDNA.[43]Together, the cDNA and its complement form adouble-stranded viral DNA that is then transported into the cell

nucleus. The integration of the viral DNA into the host cell's genome is

carried out by another viral enzyme called integrase.[42]

This integrated viral DNA may then lie dormant, in the latent stage of

HIV infection.[42]To actively produce the virus, certain cellular

transcription factors need to be present, the most important of which

is NF-B (NF kappa B), which is upregulated when T-cells become

activated.[44]This means that those cells most likely to be killed by

HIV are those currently fighting infection.

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