title: Quantitating the multiplicity of infection with human immunodeficiency virus type 1 subtype C reveals a non-poisson distribution of transmitted variants.
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.
authors.affiliation: Institute of Infectious Diseases and Molecular Medicine, Division of Medical Virology, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town 7925, South Africa.
authors.forename: M-R
authors.initials: MR
authors.lastname: Abrahams
authors.forename: J A
authors.initials: JA
authors.lastname: Anderson
authors.forename: E E
authors.initials: EE
authors.lastname: Giorgi
authors.forename: C
authors.initials: C
authors.lastname: Seoighe
authors.forename: K
authors.initials: K
authors.lastname: Mlisana
authors.forename: L-H
authors.initials: LH
authors.lastname: Ping
authors.forename: G S
authors.initials: GS
authors.lastname: Athreya
authors.forename: F K
authors.initials: FK
authors.lastname: Treurnicht
authors.forename: B F
authors.initials: BF
authors.lastname: Keele
authors.forename: N
authors.initials: N
authors.lastname: Wood
authors.forename: J F
authors.initials: JF
authors.lastname: Salazar-Gonzalez
authors.forename: T
authors.initials: T
authors.lastname: Bhattacharya
authors.forename: H
authors.initials: H
authors.lastname: Chu
authors.forename: I
authors.initials: I
authors.lastname: Hoffman
authors.forename: S
authors.initials: S
authors.lastname: Galvin
authors.forename: C
authors.initials: C
authors.lastname: Mapanje
authors.forename: P
authors.initials: P
authors.lastname: Kazembe
authors.forename: R
authors.initials: R
authors.lastname: Thebus
authors.forename: S
authors.initials: S
authors.lastname: Fiscus
authors.forename: W
authors.initials: W
authors.lastname: Hide
authors.forename: M S
authors.initials: MS
authors.lastname: Cohen
authors.forename: S Abdool
authors.initials: SA
authors.lastname: Karim
authors.forename: B F
authors.initials: BF
authors.lastname: Haynes
authors.forename: G M
authors.initials: GM
authors.lastname: Shaw
authors.forename: B H
authors.initials: BH
authors.lastname: Hahn
authors.forename: B T
authors.initials: BT
authors.lastname: Korber
authors.forename: R
authors.initials: R
authors.lastname: Swanstrom
authors.forename: C
authors.initials: C
authors.lastname: Williamson
mesh_terms: D000328:Adult; D016000:Cluster Analysis; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000635:transmission* / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D055815:Young Adult
chemical_list: D012367:RNA, Viral