Human T Cell Leukemia Virus Type 1 Infection of the Three Monocyte Subsets Contributes to Viral Burden in Humans
| Autor: | Maria Fernanda de Castro-Amarante, Maria Omsland, Giovanna S Brunetto, Katherine McKinnon, Breanna Caruso, Robyn Washington Parks, Raya Massoud, Genoveffa Franchini, Steven Jacobson, Veronica Galli, Vibeke Andresen, Cynthia A. Pise-Masison, David Venzon |
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| Rok vydání: | 2016 |
| Předmět: |
CD4-Positive T-Lymphocytes
0301 basic medicine viruses Receptor expression Immunology CD8-Positive T-Lymphocytes CCL2 Microbiology Monocytes CCL5 Receptors CCR 03 medical and health sciences 0302 clinical medicine Phagocytosis Cell Movement Virology medicine Humans CX3CL1 Receptors CXCR Human T-lymphotropic virus 1 biology Monocyte Viral Load biology.organism_classification HTLV-I Infections 030104 developmental biology medicine.anatomical_structure Insect Science DNA Viral Pathogenesis and Immunity Interleukin 19 Viral load 030217 neurology & neurosurgery |
| Zdroj: | Journal of Virology. 90:2195-2207 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.02735-15 |
| Popis: | 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. IMPORTANCE 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. |
| Databáze: | OpenAIRE |
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