Clonally expanded CD4+ T cells can produce infectious HIV-1 in vivo.

Autor: Simonetti FR; HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702; Department of Biomedical and Clinical Sciences L. Sacco, University of Milan, 20157 Milan, Italy;, Sobolewski MD; Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;, Fyne E; Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;, Shao W; Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702;, Spindler J; HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;, Hattori J; HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;, Anderson EM; HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;, Watters SA; HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;, Hill S; HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;, Wu X; Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702;, Wells D; Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702;, Su L; Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702;, Luke BT; Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702;, Halvas EK; Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;, Besson G; Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;, Penrose KJ; Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;, Yang Z; Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892;, Kwan RW; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;, Van Waes C; National Institute on Deafness and Communication Disorders Head and Neck Surgery Branch, National Institute on Deafness and Communication Disorders, National Institutes of Health, Bethesda, MD 20892; Radiation Oncology Branch, National Cancer Institute, Bethesda, MD 20892;, Uldrick T; HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, MD 20892;, Citrin DE; Radiation Oncology Branch, National Cancer Institute, Bethesda, MD 20892;, Kovacs J; Critical Care Medicine Department, National Institutes of Health Clinical Center, National Institutes of Health, Bethesda, MD 20892;, Polis MA; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;, Rehm CA; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;, Gorelick R; AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, MD 21702;, Piatak M; AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, MD 21702;, Keele BF; AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, MD 21702;, Kearney MF; HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;, Coffin JM; Department of Molecular Biology and Microbiology, Tufts University, Boston, MA 02111 john.coffin@tufts.edu fmalli@mail.nih.gov., Hughes SH; HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;, Mellors JW; Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;, Maldarelli F; HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702; john.coffin@tufts.edu fmalli@mail.nih.gov.
Jazyk: angličtina
Zdroj: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2016 Feb 16; Vol. 113 (7), pp. 1883-8. Date of Electronic Publication: 2016 Feb 08.
DOI: 10.1073/pnas.1522675113
Abstrakt: Reservoirs of infectious HIV-1 persist despite years of combination antiretroviral therapy and make curing HIV-1 infections a major challenge. Most of the proviral DNA resides in CD4(+)T cells. Some of these CD4(+)T cells are clonally expanded; most of the proviruses are defective. It is not known if any of the clonally expanded cells carry replication-competent proviruses. We report that a highly expanded CD4(+) T-cell clone contains an intact provirus. The highly expanded clone produced infectious virus that was detected as persistent plasma viremia during cART in an HIV-1-infected patient who had squamous cell cancer. Cells containing the intact provirus were widely distributed and significantly enriched in cancer metastases. These results show that clonally expanded CD4(+)T cells can be a reservoir of infectious HIV-1.
Databáze: MEDLINE