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Determining 3'-Termini and Sequences of Nascent Single-Stranded Viral DNA Molecules during HIV-1 Reverse Transcription in Infected Cells
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Published on: January 30, 2019

The B30.2(SPRY) domain of the retroviral restriction factor TRIM5alpha exhibits lineage-specific length and sequence

Byeongwoon Song1, Bert Gold, Colm O'Huigin

  • 1Dana-Farber Cancer Institute, 44 Binney Street, JFB 824, Boston, MA 02115, USA.

Journal of Virology
|April 29, 2005
PubMed

Insights

Tripartite motif (TRIM) proteins, like TRIM5alpha, provide innate immunity against retroviruses. Evolutionary changes in TRIM5alpha's B30.2 domain correlate with primate retroviral exposure, suggesting adaptation.

Area of Science:

  • Evolutionary biology
  • Immunology
  • Genetics

Background:

  • Tripartite motif (TRIM) proteins, including TRIM5alpha, are key components of the innate immune system.
  • TRIM5alpha confers intracellular resistance to retroviruses, with its B30.2(SPRY) domain being crucial for this activity, particularly in primates.
  • The B30.2 domain of TRIM5alpha exhibits significant sequence variation across primate species.

Purpose of the Study:

  • To investigate the evolutionary dynamics of the TRIM5alpha B30.2 domain in primates.
  • To identify species-specific variations and selective pressures within the B30.2 domain.
  • To correlate these evolutionary changes with historical retroviral exposures in primate lineages.

Main Methods:

  • Sequencing of nonhuman primate TRIM5 orthologs to analyze B30.2 domain variability.
  • Identification of four variable regions (v1-v4) within the B30.2 domain.
  • Phylogenetic analysis to detect lineage-specific expansions, duplications, and patterns of selection.

Main Results:

  • Observed lineage-specific expansion and duplication in the TRIM5alpha B30.2 v1 region (Old World primates) and v3 region (New World monkeys).
  • Detected substitution patterns indicative of positive selection at the borders of these variable elements.
  • Identified temporal correlations between B30.2 domain evolution and endogenous retroviral appearances in primate genomes.

Conclusions:

  • The TRIM5alpha B30.2 domain has undergone significant, punctuated evolutionary changes in primates.
  • These changes, particularly in specific variable regions, appear to be driven by selective pressures, likely from retroviral infections.
  • Findings support a role for TRIM5alpha in adaptive innate immunity against retroviruses throughout primate evolution.

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