Low-dose mucosal simian immunodeficiency virus infection restricts early replication kinetics and transmitted virus variants in rhesus monkeys.
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.
Liu
Jinyan
J
Division of Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Keele
Brandon F
BF
Li
Hui
H
Keating
Sheila
S
Norris
Philip J
PJ
Carville
Angela
A
Mansfield
Keith G
KG
Tomaras
Georgia D
GD
Haynes
Barton F
BF
Kolodkin-Gal
Dror
D
Letvin
Norman L
NL
Hahn
Beatrice H
BH
Shaw
George M
GM
Barouch
Dan H
DH
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
D018925:Chemokines; D016207:Cytokines; D012367:RNA, Viral