title: Clonally expanded CD4+ T cells can produce infectious HIV-1 in vivo.
abstract: 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.
authors: 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;
authors: Francesco R
authors: FR
authors: Simonetti
authors: Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;
authors: Michele D
authors: MD
authors: Sobolewski
authors: Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;
authors: Elizabeth
authors: E
authors: Fyne
authors: Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702;
authors: Wei
authors: W
authors: Shao
authors: HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;
authors: Jonathan
authors: J
authors: Spindler
authors: HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;
authors: Junko
authors: J
authors: Hattori
authors: HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;
authors: Elizabeth M
authors: EM
authors: Anderson
authors: HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;
authors: Sarah A
authors: SA
authors: Watters
authors: HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;
authors: Shawn
authors: S
authors: Hill
authors: Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702;
authors: Xiaolin
authors: X
authors: Wu
authors: Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702;
authors: David
authors: D
authors: Wells
authors: Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702;
authors: Li
authors: L
authors: Su
authors: Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702;
authors: Brian T
authors: BT
authors: Luke
authors: Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;
authors: Elias K
authors: EK
authors: Halvas
authors: Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;
authors: Guillaume
authors: G
authors: Besson
authors: Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;
authors: Kerri J
authors: KJ
authors: Penrose
authors: Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892;
authors: Zhiming
authors: Z
authors: Yang
authors: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
authors: Richard W
authors: RW
authors: Kwan
authors: 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;
authors: Carter
authors: C
authors: Van Waes
authors: HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, MD 20892;
authors: Thomas
authors: T
authors: Uldrick
authors: Radiation Oncology Branch, National Cancer Institute, Bethesda, MD 20892;
authors: Deborah E
authors: DE
authors: Citrin
authors: Critical Care Medicine Department, National Institutes of Health Clinical Center, National Institutes of Health, Bethesda, MD 20892;
authors: Joseph
authors: J
authors: Kovacs
authors: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
authors: Michael A
authors: MA
authors: Polis
authors: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
authors: Catherine A
authors: CA
authors: Rehm
authors: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, MD 21702;
authors: Robert
authors: R
authors: Gorelick
authors: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, MD 21702;
authors: Michael
authors: M
authors: Piatak
authors: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, MD 21702;
authors: Brandon F
authors: BF
authors: Keele
authors: HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;
authors: Mary F
authors: MF
authors: Kearney
authors: Department of Molecular Biology and Microbiology, Tufts University, Boston, MA 02111 john.coffin@tufts.edu fmalli@mail.nih.gov.
authors: John M
authors: JM
authors: Coffin
authors: HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702;
authors: Stephen H
authors: SH
authors: Hughes
authors: Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;
authors: John W
authors: JW
authors: Mellors
authors: HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702; john.coffin@tufts.edu fmalli@mail.nih.gov.
authors: Frank
authors: F
authors: Maldarelli
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D014774:Virulence; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents
keywords: HIV persistence; clonal expansion of infected cells; replication-competent HIV