Document Detail


Multiploid inheritance of HIV-1 during cell-to-cell infection.
MedLine Citation:
PMID:  21543479     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
During cell-to-cell transmission of human immunodeficiency virus type 1 (HIV-1), many viral particles can be simultaneously transferred from infected to uninfected CD4 T cells through structures called virological synapses (VS). Here we directly examine how cell-free and cell-to-cell infections differ from infections initiated with cell-free virus in the number of genetic copies that are transmitted from one generation to the next, i.e., the genetic inheritance. Following exposure to HIV-1-expressing cells, we show that target cells with high viral uptake are much more likely to become infected. Using T cells that coexpress distinct fluorescent HIV-1 variants, we show that multiple copies of HIV-1 can be cotransmitted across a single VS. In contrast to cell-free HIV-1 infection, which titrates with Poisson statistics, the titration of cell-associated HIV-1 to low rates of overall infection generates a constant fraction of the newly infected cells that are cofluorescent. Triple infection was also readily detected when cells expressing three fluorescent viruses were used as donor cells. A computational model and a statistical model are presented to estimate the degree to which cofluorescence underestimates coinfection frequency. Lastly, direct detection of HIV-1 proviruses using fluorescence in situ hybridization confirmed that significantly more HIV-1 DNA copies are found in primary T cells infected with cell-associated virus than in those infected with cell-free virus. Together, the data suggest that multiploid inheritance is common during cell-to-cell HIV-1 infection. From this study, we suggest that cell-to-cell infection may explain the high copy numbers of proviruses found in infected cells in vivo and may provide a mechanism through which HIV preserves sequence heterogeneity in viral quasispecies through genetic complementation.
Authors:
Armando Del Portillo; Joseph Tripodi; Vesna Najfeld; Dominik Wodarz; David N Levy; Benjamin K Chen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-05-04
Journal Detail:
Title:  Journal of virology     Volume:  85     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-06-23     Completed Date:  2011-09-15     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7169-76     Citation Subset:  IM    
Affiliation:
Division of Infectious Diseases, Department of Medicine, Immunology Institute, Mount Sinai School of Medicine, One Gustave Levy Place, Box 1630, New York, NY 10029, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Line
Flow Cytometry
HIV-1 / physiology*
Humans
In Situ Hybridization, Fluorescence
Polyploidy*
T-Lymphocytes / virology*
Grant Support
ID/Acronym/Agency:
5F31 A1075570//PHS HHS; A1074420//PHS HHS; DP1DA028866/DA/NIDA NIH HHS; R01 A1078783//PHS HHS
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