title: Molecular evolution analysis of the human immunodeficiency virus type 1 envelope in simian/human immunodeficiency virus-infected macaques: implications for challenge dose selection.
abstract: Since the demonstration that almost 80% of human immunodeficiency virus type 1 (HIV-1) infections result from the transmission of a single variant from the donor, biological features similar to those of HIV mucosal transmission have been reported for macaques inoculated with simian immunodeficiency virus (SIV). Here we describe the early diversification events and the impact of challenge doses on viral kinetics and on the number of variants transmitted in macaques infected with the chimeric simian/human immunodeficiency virus SHIV(sf162p4). We show that there is a correlation between the dose administered and the number of variants transmitted and that certain inoculum variants are preferentially transmitted. This could provide insight into the viral determinants of transmission and could aid in vaccine development. Challenge through the mucosal route with high doses results in the transmission of multiple variants in all the animals. Such an unrealistic scenario could underestimate potential intervention measures. We thus propose the use of molecular evolution analysis to aid in the determination of challenge doses that better mimic the transmission dynamics seen in natural HIV-1 infection.
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge, UK. Mariana.varela@glasgow.ac.uk
authors.forename: Mariana
authors.initials: M
authors.lastname: Varela
authors.forename: Lisa
authors.initials: L
authors.lastname: Landskron
authors.forename: Rachel P J
authors.initials: RP
authors.lastname: Lai
authors.forename: Trevelyan J
authors.initials: TJ
authors.lastname: McKinley
authors.forename: Willy M
authors.initials: WM
authors.lastname: Bogers
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Verschoor
authors.forename: Rob
authors.initials: R
authors.lastname: Dubbes
authors.forename: Susan W
authors.initials: SW
authors.lastname: Barnett
authors.forename: Simon D W
authors.initials: SD
authors.lastname: Frost
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Heeney
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D019143:Evolution, Molecular; D005838:Genotype; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity*; D008251:Macaca; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D016097:Simian Acquired Immunodeficiency Syndrome / Q000635:transmission / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity*; D014774:Virulence; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
chemical_list: D054299:env Gene Products, Human Immunodeficiency Virus