Multiploid inheritance of HIV-1 during cell-to-cell infection

Armando Del Portillo, Joseph Tripodi, Vesna Najfeld, Dominik Wodarz, David N. Levy, Benjamin K. Chen

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7169-7176
Number of pages8
JournalJournal of virology
Volume85
Issue number14
DOIs
StatePublished - Jul 1 2011

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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  • Cite this

    Del Portillo, A., Tripodi, J., Najfeld, V., Wodarz, D., Levy, D. N., & Chen, B. K. (2011). Multiploid inheritance of HIV-1 during cell-to-cell infection. Journal of virology, 85(14), 7169-7176. https://doi.org/10.1128/JVI.00231-11