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

Armando Del Portillo, Joseph Tripodi, Vesna Najfeld, Dominik Wodarz, David 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 2011

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Human immunodeficiency virus 1
HIV-1
inheritance (genetics)
Infection
infection
cells
proviruses
Satellite Viruses
Proviruses
viruses
T-lymphocytes
Virus Diseases
synapse
Viruses
T-Lymphocytes
Synapses
genetic complementation
cell structures
Statistical Models
titration

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Del Portillo, A., Tripodi, J., Najfeld, V., Wodarz, D., Levy, D., & 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

Multiploid inheritance of HIV-1 during cell-to-cell infection. / Del Portillo, Armando; Tripodi, Joseph; Najfeld, Vesna; Wodarz, Dominik; Levy, David; Chen, Benjamin K.

In: Journal of Virology, Vol. 85, No. 14, 07.2011, p. 7169-7176.

Research output: Contribution to journalArticle

Del Portillo, A, Tripodi, J, Najfeld, V, Wodarz, D, Levy, D & Chen, BK 2011, 'Multiploid inheritance of HIV-1 during cell-to-cell infection', Journal of Virology, vol. 85, no. 14, pp. 7169-7176. https://doi.org/10.1128/JVI.00231-11
Del Portillo A, Tripodi J, Najfeld V, Wodarz D, Levy D, Chen BK. Multiploid inheritance of HIV-1 during cell-to-cell infection. Journal of Virology. 2011 Jul;85(14):7169-7176. https://doi.org/10.1128/JVI.00231-11
Del Portillo, Armando ; Tripodi, Joseph ; Najfeld, Vesna ; Wodarz, Dominik ; Levy, David ; Chen, Benjamin K. / Multiploid inheritance of HIV-1 during cell-to-cell infection. In: Journal of Virology. 2011 ; Vol. 85, No. 14. pp. 7169-7176.
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