Low-Dose Mucosal Simian Immunodeficiency Virus Infection Restricts Early Replication Kinetics and Transmitted Virus Variants in Rhesus Monkeys

被引：99

作者：

Liu, Jinyan ^{[1
]}

Keele, Brandon F. ^{[3
]}

Li, Hui ^{[4
]}

Keating, Sheila ^{[5
,6
]}

Norris, Philip J. ^{[5
,6
]}

Carville, Angela ^{[7
]}

Mansfield, Keith G. ^{[7
]}

Tomaras, Georgia D. ^{[8
]}

Haynes, Barton F. ^{[8
]}

Kolodkin-Gal, Dror ^{[2
]}

Letvin, Norman L. ^{[2
]}

Hahn, Beatrice H. ^{[4
]}

Shaw, George M. ^{[4
]}

Barouch, Dan H. ^{[1
,9
]}

机构：

[1] Beth Israel Deaconess Med Ctr, Div Vaccine Res, Boston, MA 02215 USA

[2] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA

[3] NCI, SAIC Frederick, Frederick, MD 21702 USA

[4] Univ Alabama, Birmingham, AL 35294 USA

[5] Univ Calif San Francisco, San Francisco, CA 94118 USA

[6] Blood Syst Res Inst, San Francisco, CA 94118 USA

[7] Harvard Univ, Sch Med, New England Primate Res Ctr, Southborough, MA 01772 USA

[8] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA

[9] Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA

来源：

JOURNAL OF VIROLOGY | 2010年 / 84卷 / 19期

基金：

美国国家卫生研究院;

关键词：

HIV-1; INFECTION; DOUBLE-BLIND; VACCINE; RESPONSES; CHALLENGE; TRIAL; METAANALYSIS; SIVMAC251; MACAQUES; THAILAND;

D O I：

10.1128/JVI.01155-10

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页码：10406 / 10412

页数：7

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