Quantitating the multiplicity of infection with human immunodeficiency virus type 1 subtype C reveals a non-poisson distribution of transmitted variants

M. R. Abrahams, J. A. Anderson, E. E. Giorgi, C. Seoighe, K. Mlisana, L. H. Ping, G. S. Athreya, F. K. Treurnicht, B. F. Keele, N. Wood, J. F. Salazar-Gonzalez, T. Bhattacharya, H. Chu, I. Hoffman, S. Galvin, C. Mapanje, P. Kazembe, R. Thebus, S. Fiscus, W. HideM. S. Cohen, S. Abdool Karim, B. F. Haynes, G. M. Shaw, B. H. Hahn, B. T. Korber, R. Swanstrom, C. Williamson*

*Corresponding author for this work

Research output: Contribution to journalArticle

268 Scopus citations

Abstract

Identifying the specific genetic characteristics of successfully transmitted variants may prove central to the development of effective vaccine and microbicide interventions. Although human immunodeficiency virus transmission is associated with a population bottleneck, the extent to which different factors influence the diversity of transmitted viruses is unclear. We estimate here the number of transmitted variants in 69 heterosexual men and women with primary subtype C infections. From 1,505 env sequences obtained using a single genome amplification approach we show that 78% of infections involved single variant transmission and 22% involved multiple variant transmissions (median of 3). We found evidence for mutations selected for cytotoxic-T- lymphocyte or antibody escape and a high prevalence of recombination in individuals infected with multiple variants representing another potential escape pathway in these individuals. In a combined analysis of 171 subtype B and C transmission events, we found that infection with more than one variant does not follow a Poisson distribution, indicating that transmission of individual virions cannot be seen as independent events, each occurring with low probability. While most transmissions resulted from a single infectious unit, multiple variant transmissions represent a significant fraction of transmission events, suggesting that there may be important mechanistic differences between these groups that are not yet understood.

Original languageEnglish (US)
Pages (from-to)3556-3567
Number of pages12
JournalJournal of virology
Volume83
Issue number8
DOIs
StatePublished - Apr 2009

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Abrahams, M. R., Anderson, J. A., Giorgi, E. E., Seoighe, C., Mlisana, K., Ping, L. H., Athreya, G. S., Treurnicht, F. K., Keele, B. F., Wood, N., Salazar-Gonzalez, J. F., Bhattacharya, T., Chu, H., Hoffman, I., Galvin, S., Mapanje, C., Kazembe, P., Thebus, R., Fiscus, S., ... Williamson, C. (2009). Quantitating the multiplicity of infection with human immunodeficiency virus type 1 subtype C reveals a non-poisson distribution of transmitted variants. Journal of virology, 83(8), 3556-3567. https://doi.org/10.1128/JVI.02132-08