Human immunodeficiency virus (HIV) is a complex RNA virus of the genus Lentivirus within the Retroviridae family. HIV is an approximately 100 nm icosahedral structure with 72 external spikes that are formed by the two major envelope glycoproteins gp120 and gp41. Two major types of the AIDS virus, HIV- 1 and HIV-2, have been identified. The major serological differences reside in the surface protein gp120. HIV-1 and HIV-2 are further separated into subtypes or ‘clades’ due to the marked variability in the V3 (variable region) of the gp120 protein.
The lipid bilayer is also studded with a number of host-cell proteins during the budding process. HIV has a characteristic dense, cone-shaped nucleocapsid composed of the core protein p24. This nucleocapsid harbours two identical copies of the 9.8 kb single-stranded positive polarity RNA genome which are associated with the viral enzymes reverse transcriptase (RT), RNase H, integrase, and protease.
Human Immunodeficiency virus encodes 3 structural genes and 6 regulatory genes.
Table of Contents
Structural Components of HIV
The overall structure of HIV is spherical, with an average diameter of approximately 120 nanometers. The virus has a complex life cycle involving multiple stages, including attachment and entry into host cells, reverse transcription, integration into the host genome, replication, and release of new virions. The virus has a complex structure, primarily consisting of the following key components:
- Envelope Glycoproteins (Env): The outer part of the virus is covered by a lipid bilayer envelope. Embedded in this envelope are glycoproteins, known as Env glycoproteins (gp120 and gp41). The glycoproteins are crucial in the virus’s attachment and entry into host cells.
- Lipid Bilayer Envelope: A lipid bilayer envelope surrounds the viral core. The viral core derives from the host cell membrane during the budding process. The envelope contains viral glycoproteins and helps the virus evade the immune system.
- Matrix Protein (p17): Beneath the viral envelope is the matrix protein (p17), which helps maintain the structural integrity of the virus.
- Capsid (p24): The capsid is a protein shell that encloses the viral genomic RNA and associated enzymes. It is composed of capsid protein p24, which protects the viral RNA.
- Nucleocapsid Protein (p7 and p9): The nucleocapsid proteins p7 and p9 enclose the viral RNA into the capsid during virus assembly.
Enzymes present in HIV
- Reverse Transcriptase (RT): HIV is a retrovirus, and one of its defining features is the enzyme reverse transcriptase. This enzyme converts the viral RNA genome into DNA, allowing it to integrate into the host cell’s DNA.
- Integrase (IN): Integrase is an enzyme that helps integrate viral DNA into the host cell’s DNA. This integration is a critical step in the viral life cycle.
- Protease (PR): Protease is an enzyme that cleaves large viral polyproteins into functional proteins during the late stages of the viral life cycle. This step is crucial for the maturation of infectious virions.
Structural Genes
- Group-Specific Antigen (Gag: p24, p7, p17)
- Envelope (Env): gp 120, gp 41
- On the basis of gp120 genes, HIV is divided into subtypes (clades): A through I
- gp120 binds to CD4 on CD4+ T lymphocytes and cells of the monocyte/macrophage lineage and coreceptors (CCR5 and CXCR4)
- gp41 mediate fusion between the cellular and viral membranes.
- Polymerase (Pol): Reverse transcriptase, integrase, protease
In addition to structural genes HIV has genes whose products contribute to the complex regulation and replication of the virus. Of particular interest is the Nef (negative factor) protein. Deletions and mutations of this protein have been found in some HIV-infected individuals characterized as long-term non-progressors.
Regulatory genes found in HIV
Required for replication
- Tat: Activation of transcription of viral genes
- Rev: Transport of late mRNAs from the nucleus to the cytoplasm
Not required for replication
- Nef: Decreases CD4 and MHC class I protein expression in virus-infected cells (?mutation in the nef gene).
- Vif: Enhances viral infectivity
- Vpr: Transports viral core from the cytoplasm into the nucleus
- Vpu: Enhances virion release from the cell.
References
- Turner, B. G., & Summers, M. F. (1999). Structural biology of HIV. Journal of molecular biology, 285(1), 1–32. https://doi.org/10.1006/jmbi.1998.2354
- IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Biological Agents. Lyon (FR): International Agency for Research on Cancer; 2012. (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, No. 100B.) HUMAN IMMUNODEFICIENCY VIRUS-1. Available from: https://www.ncbi.nlm.nih.gov/books/NBK304351/
- Gelderblom, H. R., Hausmann, E. H., Ozel, M., Pauli, G., & Koch, M. A. (1987). Fine structure of human immunodeficiency virus (HIV) and immunolocalization of structural proteins. Virology, 156(1), 171–176. https://doi.org/10.1016/0042-6822(87)90449-1
Why is IT so difficult to develop a vaccine against hiv
Hi Dr Tankeshwar, would you grant permission to reproduce your figure in a PhD thesis on epidemiology of HIV (with attribution)? regards, Peter
Hi Peter
This picture is in the public domain. The original source is ‘National Institute of Allergy and Infectious Diseases, National Institutes of Health/ 2009’, you can give them credit.
Thank you Dr Tankeshwar!