title: Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection.
abstract: The precise identification of the HIV-1 envelope glycoprotein (Env) responsible for productive clinical infection could be instrumental in elucidating the molecular basis of HIV-1 transmission and in designing effective vaccines. Here, we developed a mathematical model of random viral evolution and, together with phylogenetic tree construction, used it to analyze 3,449 complete env sequences derived by single genome amplification from 102 subjects with acute HIV-1 (clade B) infection. Viral env genes evolving from individual transmitted or founder viruses generally exhibited a Poisson distribution of mutations and star-like phylogeny, which coalesced to an inferred consensus sequence at or near the estimated time of virus transmission. Overall, 78 of 102 subjects had evidence of productive clinical infection by a single virus, and 24 others had evidence of productive clinical infection by a minimum of two to five viruses. Phenotypic analysis of transmitted or early founder Envs revealed a consistent pattern of CCR5 dependence, masking of coreceptor binding regions, and equivalent or modestly enhanced resistance to the fusion inhibitor T1249 and broadly neutralizing antibodies compared with Envs from chronically infected subjects. Low multiplicity infection and limited viral evolution preceding peak viremia suggest a finite window of potential vulnerability of HIV-1 to vaccine-elicited immune responses, although phenotypic properties of transmitted Envs pose a formidable defense.
authors.affiliation: Departments of Medicine and Microbiology, University of Alabama at Birmingham, Birmingham, AL 35223, USA.
authors.forename: Brandon F
authors.initials: BF
authors.lastname: Keele
authors.forename: Elena E
authors.initials: EE
authors.lastname: Giorgi
authors.forename: Jesus F
authors.initials: JF
authors.lastname: Salazar-Gonzalez
authors.forename: Julie M
authors.initials: JM
authors.lastname: Decker
authors.forename: Kimmy T
authors.initials: KT
authors.lastname: Pham
authors.forename: Maria G
authors.initials: MG
authors.lastname: Salazar
authors.forename: Chuanxi
authors.initials: C
authors.lastname: Sun
authors.forename: Truman
authors.initials: T
authors.lastname: Grayson
authors.forename: Shuyi
authors.initials: S
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Xiping
authors.initials: X
authors.lastname: Wei
authors.forename: Chunlai
authors.initials: C
authors.lastname: Jiang
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Kirchherr
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Jeffery A
authors.initials: JA
authors.lastname: Anderson
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Ping
authors.forename: Ronald
authors.initials: R
authors.lastname: Swanstrom
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.forename: William A
authors.initials: WA
authors.lastname: Blattner
authors.forename: Paul A
authors.initials: PA
authors.lastname: Goepfert
authors.forename: J Michael
authors.initials: JM
authors.lastname: Kilby
authors.forename: Michael S
authors.initials: MS
authors.lastname: Saag
authors.forename: Eric L
authors.initials: EL
authors.lastname: Delwart
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
authors.forename: Myron S
authors.initials: MS
authors.lastname: Cohen
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Brian
authors.initials: B
authors.lastname: Gaschen
authors.forename: Gayathri S
authors.initials: GS
authors.lastname: Athreya
authors.forename: Ha Y
authors.initials: HY
authors.lastname: Lee
authors.forename: Natasha
authors.initials: N
authors.lastname: Wood
authors.forename: Cathal
authors.initials: C
authors.lastname: Seoighe
authors.forename: Alan S
authors.initials: AS
authors.lastname: Perelson
authors.forename: Tanmoy
authors.initials: T
authors.lastname: Bhattacharya
authors.forename: Bette T
authors.initials: BT
authors.lastname: Korber
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.forename: George M
authors.initials: GM
authors.lastname: Shaw
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D001483:Base Sequence; D018562:Disease Transmission, Infectious; D019143:Evolution, Molecular; D014644:Genetic Variation; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000635:transmission* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D019713:Receptors, CCR5 / Q000378:metabolism; D017423:Sequence Analysis, RNA; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D012367:RNA, Viral; D019713:Receptors, CCR5; D054299:env Gene Products, Human Immunodeficiency Virus