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      Evidence for Direct Involvement of the Capsid Protein in HIV Infection of Nondividing Cells

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          HIV and other lentiviruses can productively infect nondividing cells, whereas most other retroviruses, such as murine leukemia virus, require cell division for efficient infection. However, the determinants for this phenotype have been controversial. Here, we show that HIV-1 capsid (CA) is involved in facilitating HIV infection of nondividing cells because amino acid changes on CA severely disrupt the cell-cycle independence of HIV. One mutant in the N-terminal domain of CA in particular has lost the cell-cycle independence in all cells tested, including primary macrophages. The defect in this mutant appears to be at a stage past nuclear entry. We also find that the loss of cell-cycle independence can be cell-type specific, which suggests that a cellular factor affects the ability of HIV to infect nondividing cells. Our data suggest that CA is directly involved at some step in the viral life cycle that is important for infection of nondividing cells.

          Author Summary

          HIV and related viruses are unusual among retroviruses in their ability to replicate independently of cell-cycle progression of target cells. However, the determinants of this phenotype have been controversial. Here, we identified mutations on the surface of the capsid (CA) protein that reduce the ability of HIV to infect nondividing cells. These mutations also confer cell-cycle dependency on HIV, even in dividing cells. Interestingly, some CA mutants lose cell-cycle independence only in certain cell types. Thus, these findings suggest that a cellular factor targeting CA regulates HIV-1 infection in nondividing cells. Surprisingly, these mutations do not appear to affect nuclear localization of viral genomes, which points to a novel regulation of the cell-cycle independence of HIV by the CA protein.

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          Most cited references 31

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          A quantitative assay for HIV DNA integration in vivo.

          Early steps of infection by HIV-1 involve entry of the viral core into cells, reverse transcription to form the linear viral DNA, and integration of that DNA into a chromosome of the host. The unintegrated DNA can also follow non-productive pathways, in which it is circularized by recombination between DNA long-terminal repeats (LTRs), circularized by ligation of the DNA ends or degraded. Here we report quantitative methods that monitor formation of reverse transcription products, two-LTR circles and integrated proviruses. The integration assay employs a novel quantitative form of Alu-PCR that should be generally applicable to studies of integrating viruses and gene transfer vectors.
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            Sexual transmission and propagation of SIV and HIV in resting and activated CD4+ T cells.

            In sexual transmission of simian immunodeficiency virus, and early and later stages of human immunodeficiency virus-type 1 (HIV-1) infection, both viruses were found to replicate predominantly in CD4(+) T cells at the portal of entry and in lymphoid tissues. Infection was propagated not only in activated and proliferating T cells but also, surprisingly, in resting T cells. The infected proliferating cells correspond to the short-lived population that produces the bulk of HIV-1. Most of the HIV-1-infected resting T cells persisted after antiretroviral therapy. Latently and chronically infected cells that may be derived from this population pose challenges to eradicating infection and developing an effective vaccine.
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              HIV-1 gag proteins: diverse functions in the virus life cycle.

               Rachel Freed (1998)
              The Gag proteins of HIV-1, like those of other retroviruses, are necessary and sufficient for the assembly of virus-like particles. The roles played by HIV-1 Gag proteins during the life cycle are numerous and complex, involving not only assembly but also virion maturation after particle release and early postentry steps in virus replication. As the individual Gag domains carry out their diverse functions, they must engage in interactions with themselves, other Gag proteins, other viral proteins, lipid, nucleic acid (DNA and RNA), and host cell proteins. This review briefly summarizes our current understanding of how HIV-1 Gag proteins function in the virus life cycle.

                Author and article information

                Role: Editor
                PLoS Pathog
                PLoS Pathogens
                Public Library of Science (San Francisco, USA )
                October 2007
                26 October 2007
                : 3
                : 10
                [1 ] Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
                [2 ] Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois, United States of America
                [3 ] Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America
                Aaron Diamond AIDS Research Center, United States of America
                Author notes
                * To whom correspondence should be addressed. E-mail: memerman@ 123456fhcrc.org
                07-PLPA-RA-0284R2 plpa-03-10-16
                Copyright: © 2007 Yamashita et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                Page count
                Pages: 9
                Research Article
                In Vitro
                Homo (Human)
                Custom metadata
                Yamashita M, Perez O, Hope TJ, Emerman M (2007) Evidence for direct involvement of the capsid protein in HIV infection of nondividing cells. PLoS Pathog 3(10): e156. doi: 10.1371/journal.ppat.0030156

                Infectious disease & Microbiology


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