Overview
AIDS (acquired immunodeficiency syndrome) is the late stage of infection with the human immunodeficiency virus (HIV), a retrovirus that infects and destroys CD4+ T helper cells. Loss of these cells leads to profound immunosuppression, opportunistic infections and tumours.
Aetiology and transmission
Acquired immunodeficiency syndrome (AIDS) is a retroviral disease caused by the human immunodeficiency virus (HIV). We see depletion of CD4+ T-lymphocytes and profound immunosuppression. Sexual transmission is the most common method of transmission, viruses are present in semen (cellulary and extracellularly), and enters the body through mucosal abrasions, HIV is also present in vaginal and cervical cells of women so can be spread females to males (although 8x less likely). Transmission can also be via IV drug abusers, transmission of infected blood and mother to infant transmission.
HIV is a lentivirus and has two genetic variants (HIV 1 and HIV 2, 1 being the most common).
HIV structure and replication
Structure. HIV is an enveloped RNA virus of the genus Lentivirus (family Retroviridae).
- The virion contains two identical copies of single-stranded RNA and the enzymes reverse transcriptase, integrase and protease, inside a conical capsid (p24) surrounded by a matrix protein (p17).
- The lipid envelope, taken from the host cell, carries the glycoproteins gp120 (binds CD4 and the coreceptor) and gp41 (mediates fusion).
- The genome has the three structural genes gag (capsid and matrix), pol (enzymes) and env (envelope), and several regulatory genes.
Replication. The steps are: attachment of gp120 to CD4 and a coreceptor and fusion of the envelope; release of the RNA into the cytoplasm; reverse transcription of RNA into DNA; integration of the proviral DNA into the host genome by integrase; transcription and translation of viral proteins; cleavage of the polyproteins by protease; assembly and budding of new virions.
The main target for the virus is the immune system and CNS. Here is the lifecycle of the virus:
- HIV binds to CD4 and a coreceptor (CCR5 or CXCR4) on T-cells or macrophages causing conformational change allowing HIV to enter the cell
- Once internalised, the viral genome undergoes reverse transcription, in active T-lymphocytes this becomes proviral DNA, which is
- integrated into the host genome where it can remain latent for years
- Once it becomes translated, there is extensive viral replication and CD4+ cell lysis, causing destruction of lymphoid tissue and depletion of CD4+ T-cells