title: Human T Cell Leukemia Virus Type 1 Infection of the Three Monocyte Subsets Contributes to Viral Burden in Humans.
abstract: Because the viral DNA burden correlates with disease development, we investigated the contribution of monocyte subsets (classical, intermediate, and nonclassical monocytes) to the total viral burden in 22 human T cell leukemia virus type 1 (HTLV-1)-infected individuals by assessing their infectivity status, frequency, as well as chemotactic and phagocytic functions. All three monocyte subsets sorted from HTLV-1-infected individuals were positive for viral DNA, and the frequency of classical monocytes was lower in the blood of HTLV-1-infected individuals than in that of uninfected individuals, while the expression levels of the chemokine receptors CCR5, CXCR3, and CX3CR1 in classical monocytes were higher in HTLV-1-infected individuals than uninfected individuals; the percentage of intermediate monocytes and their levels of chemokine receptor expression did not differ between HTLV-1-infected and uninfected individuals. However, the capacity of intermediate monocytes to migrate to CCL5, the ligand for CCR5, was higher, and a higher proportion of nonclassical monocytes expressed CCR1, CXCR3, and CX3CR1. The level of viral DNA in the monocyte subsets correlated with the capacity to migrate to CCL2, CCL5, and CX3CL1 for classical monocytes, with lower levels of phagocytosis for intermediate monocytes, and with the level of viral DNA in CD8(+) and CD4(+) T cells for nonclassical monocytes. These data suggest a model whereby HTLV-1 infection augments the number of classical monocytes that migrate to tissues and become infected and the number of infected nonclassical monocytes that transmit virus to CD4(+) and CD8(+) T cells. These results, together with prior findings in a macaque model of HTLV-1 infection, support the notion that infection of monocytes by HTLV-1 is likely a requisite for viral persistence in humans.
  
  
  OBJECTIVE
  Monocytes have been implicated in immune regulation and disease progression in patients with HTLV-1-associated inflammatory diseases. We detected HTLV-1 DNA in all three monocyte subsets and found that infection impacts surface receptor expression, migratory function, and subset frequency. The frequency of nonclassical patrolling monocytes is increased in HTLV-1-infected individuals, and they have increased expression of CCR1, CXCR3, and CX3CR1. The viral DNA level in nonclassical monocytes correlated with the viral DNA level in CD4(+) and CD8(+) T cells. Altogether, these data suggest an increased recruitment of classical monocytes to inflammation sites that may result in virus acquisition and, in turn, facilitate virus dissemination and viral persistence. Our findings thus provide new insight into the importance of monocyte infection in viral spread and suggest targeting of monocytes for therapeutic intervention.
authors.affiliation: Animal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: Maria Fernanda
authors.initials: MF
authors.lastname: de Castro-Amarante
authors.affiliation: Animal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, Bethesda, Maryland, USA masisonc@mail.nih.gov franchig@mail.nih.gov.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Pise-Masison
authors.affiliation: Animal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: McKinnon
authors.affiliation: Animal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: Robyn
authors.initials: R
authors.lastname: Washington Parks
authors.affiliation: Animal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: Veronica
authors.initials: V
authors.lastname: Galli
authors.affiliation: Animal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, Bethesda, Maryland, USA Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, Translational Hemato-Oncology Group, University of Bergen, Bergen, Norway.
authors.forename: Maria
authors.initials: M
authors.lastname: Omsland
authors.affiliation: Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, Translational Hemato-Oncology Group, University of Bergen, Bergen, Norway.
authors.forename: Vibeke
authors.initials: V
authors.lastname: Andresen
authors.affiliation: Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.
authors.forename: Raya
authors.initials: R
authors.lastname: Massoud
authors.affiliation: Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Brunetto
authors.affiliation: Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.
authors.forename: Breanna
authors.initials: B
authors.lastname: Caruso
authors.affiliation: Biostatistics and Data Management Section, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.affiliation: Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Jacobson
authors.affiliation: Animal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, Bethesda, Maryland, USA masisonc@mail.nih.gov franchig@mail.nih.gov.
authors.forename: Genoveffa
authors.initials: G
authors.lastname: Franchini
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D004279:DNA, Viral / Q000032:analysis / Q000302:isolation & purification; D015490:HTLV-I Infections / Q000821:virology*; D015368:Human T-lymphotropic virus 1 / Q000302:isolation & purification*; D006801:Humans; D009000:Monocytes / Q000737:chemistry / Q000821:virology*; D010587:Phagocytosis; D054388:Receptors, CCR / Q000032:analysis; D054387:Receptors, CXCR / Q000032:analysis; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D054388:Receptors, CCR; D054387:Receptors, CXCR