HIV, or human immunodeficiency virus, is a retrovirus that infects and destroys the immune system's CD4+ T cells, leading to acquired immunodeficiency syndrome (AIDS). But how does this tiny virus manage to invade cells and cause so much damage? Here's an overview of HIV's invasion process and replicative life cycle inside human cells.

Credit NIAID

Binding

It all starts when HIV encounters a target cell expressing the CD4 receptor and either the CCR5 or CXCR4 co-receptors on its surface. The gp120 protein on HIV's outer envelope recognizes and binds to CD4, triggering conformational changes that allow gp120 to also bind the co-receptor.

Fusion

This activates the gp41 protein to insert its hydrophobic fusion peptide into the cell membrane, pulling the viral and cell membranes together. The membranes fuse, allowing the inner viral core to enter the cell's cytoplasm.

Reverse Transcription

Once inside, the single-stranded viral RNA genome is reverse transcribed into double-stranded DNA by the enzyme reverse transcriptase. This viral DNA enters the cell nucleus and integrates into the host chromosome with the help of integrase enzyme. The integrated viral DNA, called a provirus, can lie dormant for years until the cell becomes activated.

Transcription and Translation

When the host cell activates, cellular proteins recognize promoter sequences in the provirus and begin transcribing the viral genes. New viral RNA, proteins, and genomes are produced and assembled at the cell membrane.

Budding and Maturation

Immature non-infectious virions pinch off from the cell in a process called budding. The virions then undergo maturation mediated by the viral protease, which cleaves polyproteins to form structurally mature infectious virions ready to invade new cells.

HIV replicates rapidly, mutates frequently, and can evade immune defenses, allowing it to persist in the body. Ongoing research seeks to better understand each stage of the HIV life cycle to find new therapeutic targets. Stopping viral entry, reverse transcription, integration, or maturation could effectively control HIV infection. As we continue learning how this cunning virus operates, we edge closer to outsmarting it.

Reference

Wilen, C. B., Tilton, J. C. & Doms, R. W. HIV: Cell Binding and Entry. Cold Spring Harbor Perspectives in Medicine 2, a006866–a006866 (2012).

Freed, E. O. HIV-1 Replication. Somatic Cell and Molecular Genetics 26, 13–33 (2001).

Ferguson, M. R., Rojo, D. R., Von Lindern, J. J. & O’Brien, W. A. HIV-1 replication cycle. Clinics in Laboratory Medicine 22, 611–635 (2002).