HIV

HIV is a member of the lentivirus group within the Retroviridae family. This RNA virus is believed to have originated from a cross-species transmission of the SIV to humans. The molecular phylogeny of HIV reveals a complex history of viral evolution and adaptation. HIV exists in two main types: HIV-1, more virulent and globally prevalent, and HIV-2, mostly confined to West Africa. HIV has multiple different circulating strains and can undergo tropism switching within a single host in large part due to the highly error prone viral reverse transcriptase enzyme conferring a high degree of mutagenesis. Each strain has differential resistance to different anti-retroviral therapy drugs. Their genetic divergence is a subject of extensive molecular study, providing insights into viral evolution and pathogenicity. 

Viral Structure

Genomic Structure

HIV possesses a unique RNA genome of approx 9.8 kb comprising nine genes: gag, pol, env, tat, rev, nef, vif, vpr, and vpu. These genes encode for both structural and functional proteins essential for the virus's life cycle. These genes encode structural, regulatory, and accessory proteins, each playing a critical role in the virus's life cycle and interaction with the host. The gag gene encodes core and matrix proteins, pol for enzymes essential for viral replication, and env for envelope glycoproteins. The complex regulation of these genes, including mechanisms of splicing and translation, is a focal point of molecular research in HIV. The focus is on the unique arrangement of overlapping genes and the use of alternative splicing mechanisms, which allow HIV to encode multiple proteins from a single RNA transcript.

Protein Components

The HIV envelope glycoproteins, gp120 and gp41, are pivotal for virus entry into host cells. gp120 binds to the CD4 receptor on host immune cells, primarily T lymphocytes, and facilitates attachment. This binding induces structural changes, enabling gp41 to mediate fusion between the viral and cellular membranes. The structural proteins p24, p17, and p7, form the viral capsid and play roles in viral assembly and integrity.

Viral Enzymes

The pol gene encodes three critical enzymes: reverse transcriptase (RT), integrase (IN), and protease (PR). RT catalyzes the reverse transcription of viral RNA into DNA, a process characterised by a high error rate contributing to the virus's genetic variability. RT is highly error prone in large part due to its lack of proofreading capability, which paradoxically allows better evasion of the immune system, anti-retroviral drug resistance and difficulty with vaccine development. IN is responsible for the integration of viral DNA into the host genome, a step crucial for viral replication and persistence. PR processes the viral precursor proteins into functional units, essential for viral maturation and infectivity.

Life Cycle

Attachment and Fusion

A

Reverse Transcription

B

Integration

C

Replication

C

Assembly and Budding

C