title: Low-dose mucosal simian immunodeficiency virus infection restricts early replication kinetics and transmitted virus variants in rhesus monkeys.
abstract: Defining the earliest virologic events following human immunodeficiency virus type 1 (HIV-1) transmission may be critical for the design of vaccine strategies aimed at blocking acquisition of HIV-1 infection. In particular, the length of the eclipse phase and the number of transmitted virus variants may define the window in which a prophylactic vaccine must act. Here we show that the dose of the virus inoculum affects these key virologic parameters following intrarectal simian immunodeficiency virus (SIV) infection of rhesus monkeys. Low-dose SIV infection resulted in a lengthened eclipse phase, fewer transmitted virus variants, and decreased innate immune activation compared with these parameters in high-dose SIV infection. These data suggest a mechanism by which it may be considerably easier for a vaccine to protect against low-risk HIV-1 transmission than against high-risk HIV-1 transmission. These findings have implications for the design and interpretation of HIV-1 vaccine efficacy studies.
authors.affiliation: Division of Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Liu
authors.forename: Brandon F
authors.initials: BF
authors.lastname: Keele
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Sheila
authors.initials: S
authors.lastname: Keating
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Norris
authors.forename: Angela
authors.initials: A
authors.lastname: Carville
authors.forename: Keith G
authors.initials: KG
authors.lastname: Mansfield
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Dror
authors.initials: D
authors.lastname: Kolodkin-Gal
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.forename: George M
authors.initials: GM
authors.lastname: Shaw
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
mesh_terms: D000818:Animals; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D015752:Genes, env; D014644:Genetic Variation; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control / Q000635:transmission; D015497:HIV-1; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000276:immunology / Q000821:virology; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D012007:Rectum / Q000276:immunology / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000635:transmission / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*; D013997:Time Factors; D014779:Virus Replication
chemical_list: D018925:Chemokines; D016207:Cytokines; D012367:RNA, Viral