Viral infection- Human immunodeficiency virus

The Life Cycle of HIV

1) Attachment and entry

When HIV gains entry to a cell, the method of producing new viruses begins. Attachment and fusion are the two main stages of this process.

Having a CD4 receptor on the surface of HIV infects immune system cells. The cells also involve T-lymphocytes (t cells), monocytes, macrophages, and dendritic cells. The CD4 receptor is utilized by the cell to signal to other parts of the immune system the presence of antigens.

When a CD4 cell comes during contact with an HIV, the gp120 spikes on the surface of HIV lock onto the CD4 receptor and also on co-receptor (CCR or CXCR). The gp41 protein is used to merge the HIV envelope with the cell wall. This method of fusion permits HIV capsid to enter the CD4 cell.

Different types of antiretroviral drug have been developed to block different stages of the processes of attachment and entry:

• CCR5 inhibitor
• Attachment inhibitor
• Fusion inhibitor

The gp41 and gp120 proteins on the surface of the virus are also targets for vaccines that are designed to produce antibody responses.

2) Reverse transcription

Before the mixing into the DNA of the host cell the HIV RNA, when entered the cell must be `reverse-transcribed` into proviral DNA. HIV utilizes its reverse transcriptase enzyme to convert RNA into proviral DNA within the cell.

Two types of antiretroviral drug have been developed to prevent the action of reverse transcriptase and the creation of proviral DNA:

• Nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs and NtRTIs) block HIV production by inserting a nucleoside or nucleotide into the chain of HIV DNA because it is created, terminating the chain.

NNRTIs (Non-nucleoside reverse transcriptase inhibitors) block HIV production by binding onto the reverse transcriptase enzyme.

3) Integration

Once the proviral DNA enters into the cell nucleus, then it binds to the host DNA and then the HIV DNA strand is inserted into the host cell DNA.

HIV integrase inhibitors are developed to block the transfer of the HIV DNA strand into the host cell DNA.

After the proviral DNA is integrated into the DNA of the host cell, HIV remains inactive within the cellular DNA. This stage is called latency and therefore cell is described as ‘latently infected’. It is often difficult to identify these latently infected cells even when using the most sensitive tests.

4) Transcription and Translation

If the cell will receive a signal to become active, it will produce HIV RNA. If they encounter an infectious agent CD4 cells become activated.

HIV uses the host enzyme RNA polymerase to form messenger RNA When the cell becomes active. For producing new viral proteins in long chains, the instructions are provided by the messenger RNA.

The HIV proteins of long chains are cut into smaller chains by HIV’s protease enzyme.

5) Assembly and budding

• HIV protease inhibitors are arranged to block the activity of HIV’s protease enzyme.

As the virus buds from the cell wall, its genome becomes placed within a capsid produced from HIV’s gag protein. After the new virus is assembled, it must leave the cell by getting aggressive towards the cell wall. To leave the cell completely and become infectious, the virus must take lipids from the cell wall to form the surface glycoproteins.

• Maturation inhibitors are being produced to block the cutting of the gag protein that is needed to create a mature virus.