期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 112, 期 12, 页码 E1480-E1489出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1421607112
关键词
HIV-1; Gag; replicative capacity; immune activation; pathogenesis
资金
- Kiran Gill and Barbara Cervasi at the Emory Vaccine Center/Emory Center for AIDS Research Flow Core [P30 AI050409]
- National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID, NIH) [R01 AI64060, R37 AI51231]
- Virology Core at the Emory Center for AIDS Research from the NIAID, NIH [P30 AI050409]
- Yerkes National Primate Research Center Base Grant through the National Center for Research Resources [2P51RR000165-51, P51RR165]
- Office of Research Infrastructure Programs/OD [P51OD11132]
- International AIDS Vaccine Initiative (IAVI)
- Bill AMP
- Melinda Gates Foundation
- Ministry of Foreign Affairs of Denmark
- Irish Aid
- Ministry of Finance of Japan
- Ministry of Foreign Affairs of the Netherlands
- Norwegian Agency for Development Cooperation
- UK Department for International Development
- US Agency for International Development (USAID)
- Action Cycling Fellowships
HIV-1 infection is characterized by varying degrees of chronic immune activation and disruption of T-cell homeostasis, which impact the rate of disease progression. A deeper understanding of the factors that influence HIV-1-induced immunopathology and subsequent CD4(+) T-cell decline is critical to strategies aimed at controlling or eliminating the virus. In an analysis of 127 acutely infected Zambians, we demonstrate a dramatic and early impact of viral replicative capacity (vRC) on HIV-1 immunopathogenesis that is independent of viral load (VL). Individuals infected with high-RC viruses exhibit a distinct inflammatory cytokine profile as well as significantly elevated T-cell activation, proliferation, and CD8(+) T-cell exhaustion, during the earliest months of infection. Moreover, the vRC of the transmitted virus is positively correlated with the magnitude of viral burden in naive and central memory CD4(+) T-cell populations, raising the possibility that transmitted viral phenotypes may influence the size of the initial latent viral reservoir. Taken together, these findings support an unprecedented role for the replicative fitness of the founder virus, independent of host protective genes and VL, in influencing multiple facets of HIV-1-related immunopathology, and that a greater focus on this parameter could provide novel approaches to clinical interventions.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据