Nonrandom HIV-1 infection and double infection via direct and cell-mediated pathways

被引:76
作者
Dang, Q
Chen, JB
Unutmaz, D
Coffin, JM
Pathak, VK
Powell, D
KewalRamani, VN
Maldarelli, F
Hu, WS
机构
[1] NCI, HIV Drug Resistance Program, Ft Detrick, MD 21702 USA
[2] NCI, Data Management Serv, Ft Detrick, MD 21702 USA
[3] W Virginia Univ, Sch Med, Dept Microbiol Immunol & Cell Biol, Morgantown, WV 26506 USA
[4] Vanderbilt Univ, Dept Microbiol & Immunol, Nashville, TN USA
关键词
D O I
10.1073/pnas.0307636100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cells infected with two related retroviruses can generate heterozygous virions, which are the precursors of recombinant proviruses. Although many studies have focused on the frequencies and mechanisms of retroviral recombination, little is known about the dynamics of double infection. To examine this issue, viruses generated from two HIV-11 vectors containing different markers were mixed together, and were used to infect target cells. The numbers of cells expressing none, one, or both markers were measured and were used to calculate whether double infection occurred at frequencies expected from random infection events. We found that double infection occurred significantly more frequently than predicted from random distribution; increased rates of double infection were observed in both a T cell line and primary activated CD4(+) T cells. In addition to direct virus infection, we also examined the nature of cell-mediated HIV-1 double infection. Increased double infection was observed in all experiments regardless of whether a cell line or primary human dendritic cells were used for capture and transmission of HIV-1. Therefore, our results indicate that HIV-1 double infection occurs more frequently than it would at random in both direct and cell-mediated HIV-1 infections. To our knowledge, this is the first direct evidence of nonrandom double infection in HIV-1. Frequent double HIV-1 infections in infected individuals would allow the generation of recombinant viruses that could then affect their pathogenesis and evolution.
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页码:632 / 637
页数:6
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