Abstract/Details

Cell-to-cell spread of HIV-1 via virological synapses


2010 2010

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Abstract (summary)

Human Immunodeficiency Virus, type 1 (HIV-1) primarily infects CD4+ T cells and macrophages, which leads to an acquired immunodeficiency syndrome (AIDS). HIV-1 can infect cells through cell-free or cell-associated routes. While infection by cell-free virus has been studied extensively, cell-to-cell infection has only recently been appreciated between CD4+ T cells. Here it is shown that HIV-1 spreads from cell-to-cell from macrophages to CD4+ T cells, and that cell-to-cell infection can result in a multi-copy infection. In order to study cell-to-cell infection, the laboratory of Benjamin Chen developed an infectious molecular clone of HIV-1 that labels the Gag protein internally with the green fluorescent protein (GFP), called HIV Gag-iGFP. Labeling Gag in this manner recapitulates intracellular Gag localization in mammalian cells by immunofluorescence. Using this strategy to track HIV-1 assembly and the virus particles themselves, macrophages were found to form virological synapses with autologous CD4+ T cells and transferred HIV-1 particles to them. The multiplicity of infection in CD4+ T cells by either a cell-free or a cell-to-cell route was evaluated as well as how the co-infection frequency changes as the overall infection frequency changes by both routes. In contrast to cell-free infection, which followed a random, Poisson distribution, cell-to-cell infection produced multi-copy infected cells at a frequency proportional to the infection frequency. Direct fluorescence in situ hybridization revealed more proviral DNA copies in the nuclei of infected cells following a cell-to-cell infection than a cell-free infection. Altogether, these data indicate that cell-to-cell infection occurs between different types of cells in the immune system and that cell-to-cell infection allows for multi-copy infection, which may act to increase viral diversity by buffering less-fit mutants through complementation.

Indexing (details)


Subject
Virology
Classification
0720: Virology
Identifier / keyword
Biological sciences; Cell to cell spread; Complementation; HIV-1; Pseudodiploids; Virological synapses
Title
Cell-to-cell spread of HIV-1 via virological synapses
Author
Del Portillo, Armando
Number of pages
124
Publication year
2010
Degree date
2010
School code
1353
Source
DAI-B 71/10, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9781124214894
Advisor
Tortorella, Domenico
Committee member
Basler, Christopher; Evans, Matthew; Hioe, Catarina
University/institution
Mount Sinai School of Medicine of New York University
Department
Microbiology
University location
United States -- New York
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3422409
ProQuest document ID
758398204
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/758398204
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