Viral genetic evolution in macaques infected with molecularly cloned simian immunodeficiency virus correlates with

V M Hirsch1, G Dapolito, A Hahn

  • 1Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Twinbrook II Facility, Rockville, Maryland 20852, USA. vhirsch@atlas.niaid.nih.gov

Journal of Virology
|July 11, 1998
PubMed

Insights

Persistent simian immunodeficiency virus (SIV) replication drives genetic evolution of the SIV envelope glycoprotein, particularly in progressor macaques. Nonprogressors showed varied viral evolution despite good containment.

Area of Science:

  • Virology
  • Immunology
  • Primate Models

Background:

  • Simian immunodeficiency virus (SIV) is a lentivirus that infects non-human primates.
  • SIV infection in macaques serves as a model for human immunodeficiency virus (HIV) pathogenesis.
  • Understanding SIV evolution is crucial for developing effective antiviral strategies.

Purpose of the Study:

  • To investigate the genetic evolution of the SIV envelope glycoprotein in macaques.
  • To correlate envelope evolution with viremia patterns and disease progression.
  • To identify factors influencing SIV genetic diversity.

Main Methods:

  • Infection of six macaques (Macaca nemestrina) with SIVsm62d.
  • Monitoring of plasma viremia and disease outcome.
  • Genetic sequencing and analysis of the SIV envelope V1 region.
  • Measurement of homologous neutralizing antibody titers.

Main Results:

  • Two progressor macaques developed AIDS, exhibiting higher viremia and more extensive V1 envelope evolution than four nonprogressors.
  • Nonprogressor macaques displayed significant individual variability in viremia and V1 envelope genetic evolution.
  • Persistent viral replication correlated with increased mutation and evolution in the SIV envelope V1 region.

Conclusions:

  • Persistent SIV replication is a critical driver of SIV envelope genetic evolution.
  • Individual host responses and viral dynamics significantly influence SIV evolution.
  • The V1 region of the SIV envelope is a key site of adaptive evolution during infection.

Related Concept Videos

Viral Mutations00:36

Viral Mutations

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material for adaptive...
Size and Structure of Viral Genomes01:26

Size and Structure of Viral Genomes

Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
Retrovirus Life Cycles01:10

Retrovirus Life Cycles

Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the retrovirus to...
Retroviruses02:33

Retroviruses

Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
Viral Recombination00:57

Viral Recombination

Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.