The Lifecycle of Retrovirus

Lifecycle of Retrovirus

Introduction

Retroviruses are a type of RNA virus that replicate through a DNA intermediate. They integrate their genetic material into the host genome, enabling efficient replication. This lifecycle ensures their persistence and spread in host populations.

Source: Biorender.com [6,7]

Binding

The first step in the retrovirus life cycle is the binding of the virus to the host cell. This binding is mediated by specific viral surface proteins interacting with receptors on the host cell surface.

The list of specific receptors is provided in Table 1.

Table 1. List of Specific Receptors in Retroviruses

Name of Virus	Name of Receptor	References
Ecotropic MLV	CAT-1 (amino-acid transporter)	[1,10]
HIV	CD4 (T-cell surface marker)	[2]
HTLV	GLUT-1 (glucose transporter)	[3]
Amphotropic MLV	PIT-2 (phosphate transporter)	[4,9]
Gibbon Ape Leukemia Virus (GaLV)	PIT-1 (phosphate transporter)	[5]

Fusion

After binding to the host cell, the retrovirus must enter the host cell's cytoplasm to initiate infection. This is achieved through the fusion of the viral envelope with the host cell membrane. Fusion allows the viral core containing the viral RNA and associated enzymes to enter the host cell.

Reverse Transcription

Once inside the host cell, the retroviral RNA genome is reverse transcribed into double-stranded DNA by the viral enzyme reverse transcriptase. This process involves the synthesis of a complementary DNA (cDNA) strand from the viral RNA template, followed by the synthesis of a second DNA strand to form a double stranded DNA molecule. Reverse transcription takes place within the cytoplasm of the host cell.

Integration

The newly synthesized viral DNA is transported into the nucleus of the host cell, where it integrates into the host cell's chromosomal DNA. This integration is mediated by the viral enzyme integrase, which cleaves the host cell DNA and inserts the viral DNA into the host genome. Once integrated, the viral DNA is referred to as a provirus.

Transcription

Once integrated into the host genome, the proviral DNA can be transcribed by the host cell's RNA polymerase machinery. This results in the synthesis of viral messenger RNA (mRNA) transcripts, which can then be translated into viral proteins.

Translation

The viral mRNA transcripts produced by the host cell are translated by the host cell's ribosomes into viral proteins. These viral proteins include structural proteins (such as capsid proteins) and enzymes required for viral replication.

Assembly

The newly synthesized viral proteins and viral RNA molecules are assembled into new virus particles, or virions, within the cytoplasm of the host cell. The structural proteins encapsulate the viral RNA to form the viral core, while other viral proteins contribute to the formation of the viral envelope.

Budding

Once assembled, the new virus particles bud from the host cell membrane, acquiring a lipid envelope derived from the host cell membrane embedded with viral glycoproteins. This budding process allows the newly formed virus particles to acquire their final structure and become infectious.

Release

The mature virus particles are released from the host cell, either by budding off from the cell surface or through cell lysis, where the host cell is destroyed, releasing the viral particles into the extracellular environment. These released virus particles can then infect new host cells, continuing the cycle of infection.

Conclusion

This complete cycle allows retroviruses to efficiently infect host cells, replicate their genetic material, and produce new virus particles, facilitating the spread of infection within a host organism and between individuals.

References

1. Kim JW, Closs EI, Albritton LM, Cunningham JM. Transport of cationic amino acids by the mouse ecotropic retrovirus receptor. Nature. 1991;352:725–728.

2. Maddon PJ, Dalgleish AG, McDougal JS, et al. The T4 gene encodes the AIDS virus receptor. Cell. 1986;47:333–348.

3. Manel N, Kim FJ, Kinet S, et al. The ubiquitous glucose transporter GLUT-1 is a receptor for HTLV. Cell. 2003;115:449–459.

4. Miller DG, Miller AD. A family of retroviruses that utilize related phosphate transporters for cell entry. J Virol. 1994;68:8270–8276.

5. O'Hara B, Johann SV, Klinger HP, et al. Characterization of a human gene conferring sensitivity to infection by gibbon ape leukemia virus. Cell Growth Differ. 1990;1:119–127.

6. Origin of viruses. Nature.

7. Team, B. (2020). Retrovirus Life Cycle. BioRender.

8. Van Zeijl M, Johann SV, Closs E, et al. A human amphotropic retrovirus receptor is a member of the gibbon ape leukemia virus receptor family. Proc Natl Acad Sci U S A. 1994;91:1168–1172.