HIV Essentials

Human Immunodeficiency virus (HIV)

Key concepts Human Immunodeficiency virus (HIV) is the virus that causes AIDS.

HIV is a single-stranded RNA virus, specifically a retrovirus. It is a member of the Lentivirus, family Retroviridae.

Retroviruses have an RNA to DNA step in their life cycle. They encode a reverse transcriptase enzyme to accomplish this step.

HIV is an enveloped virus.

HIV causes a progressive loss of CD4 T cells, which are necessary for proper immune function, and thus destroys the immune system's ability to combat infection. It is the secondary infections from immune suppression that are the most harmful to the patient (not the HIV virus, itself).

HIV Virion Structure

Viral capsid structure, made up of the p24 protein.

Viral RNA. HIV has two copies of its genome.

Along the RNA, we draw nucleocapsid protein (p7 protein). This protein is important for viral RNA translation and packaging. Integrase and reverse transcriptase proteins are also in the capsid; these are necessary for the RNA genome of HIV to enter the host DNA.

The viral envelope is made up of host cellular membrane lipids and proteins; it fuses with the host plasma membrane during infection.

Viral matrix protein (p17 protein) is within the inner layer of the viral envelope.

Viral protease is in the matrix. It is necessary for the maturation of the virus: it cleaves a precursor polypeptide to produce key proteins.

Envelope spikes travel from the matrix through the envelope. The envelope spike is made of three gp41/gp120 heterodimers.

The HIV life cycle

HIV recognizes a specific receptor on the surface of cells, the CD4 receptor and requires a co-receptor for infection. The co-receptor is generally either CCR5 or CXCR4.

Step 1: Attachment

The HIV virion binds to the cell via the interaction between gp120 and CD4.

Step 2: Fusion

The HIV envelope fuses with the plasma membrane, which allows the capsid and HIV proteins access to the cell.

##Step 3: Reverse Transcription Reverse transcriptase converts the RNA into double-stranded DNA.

Step 4: Integration

Viral DNA is now a part of the host's DNA because of the integrase enzyme. From here, every time the cell replicates, the HIV viral genome is replicated as well. A signal can then reactivate the viral genome and produce viral gene transcription.

Step 5: Gene expression.

Viral genomic RNA is transcribed from the integrated viral genome. Viral mRNA is transcribed to be translated into viral proteins.

Step 6: Viral assembly.

Various parts of the virus begin to come together.

Step 7: Budding.

Draw the virus beginning to bud from the cell surface.
Draw the protease within this budding virus.

The capsid, nucleocapsid, and matrix proteins are not noticeable because they are still part of a precursor polypeptide and need to be cleaved before they can function.

Step 8: Maturation.

Draw the mature HIV virion with the capsid present.

The protease cleaves the polypeptide to produce the capsid, nucleocapsid, and matrix proteins.

Pharmacologic correlations

Highly Active Antiretroviral Therapy (HAART).

HAART treatment utilizes multiple drugs that act on different targets during the HIV life cycle.

Co-receptor antagonists act at step 1 (attachment) of the life cycle.

They block HIV's ability to use co-receptors. As an example, the drug maraviroc blocks CCR5.

Fusion inhibitors (ex, enfuvirtide)

Act at step 2 (fusion).

Reverse transcriptase inhibitors

Work at step 3 (reverse transcription).

There are two main types of reverse transcriptase inhibitors:

Nucleoside reverse transcriptase inhibitors (NRTIs) Ex: AZT and non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as efavirenz.
There are also nucleotide reverse transcriptase inhibitors, but their method of action is essentially the same as the nucleoside reverse transcriptase inhibitors.

Integrase inhibitors

Work at step 4 (integration). Ex. Raltegravir

Protease inhibitors

Work at step 8 (maturation). Ex: Indinavir

HIV Essentials

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