In Vivo HIV-1 Cell-to-Cell Transmission Promotes Multicopy Micro-compartmentalized Infection.
HIV-1 infection is enhanced by adhesive structures that form between infected and uninfected T cells called virological synapses (VSs). This mode of transmission results in the frequent co-transmission of multiple copies of HIV-1 across the VS, which can reduce sensitivity to antiretroviral drugs. Studying HIV-1 infection of humanized mice, we measured the frequency of co-transmission and the spatiotemporal organization of infected cells as indicators of cell-to-cell transmission in vivo. When inoculating mice with cells co-infected with two viral genotypes, we observed high levels of co-transmission to target cells. Additionally, micro-anatomical clustering of viral genotypes within lymphoid tissue indicates that viral spread is driven by local processes and not a diffuse viral cloud. Intravital splenic imaging reveals that anchored HIV-infected cells induce arrest of interacting, uninfected CD4(+) T cells to form Env-dependent cell-cell conjugates. These findings suggest that HIV-1 spread between immune cells can be anatomically localized into infectious clusters.
Division of Infectious Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Kenneth M
KM
Law
Department of Ecology and Evolutionary Biology and Department of Mathematics, University of California, Irvine, Irvine, CA 92697, USA.
Natalia L
NL
Komarova
Division of Infectious Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Alice W
AW
Yewdall
Division of Infectious Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Rebecca K
RK
Lee
Division of Infectious Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Olga L
OL
Herrera
Department of Ecology and Evolutionary Biology and Department of Mathematics, University of California, Irvine, Irvine, CA 92697, USA.
Dominik
D
Wodarz
Division of Infectious Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: benjamin.chen@mssm.edu.
Benjamin K
BK
Chen
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002465:Cell Movement; D002474:Cell-Free System; D002478:Cells, Cultured; D018628:Gene Dosage; D015658:HIV Infections / Q000097:blood / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D054992:Immunological Synapses / Q000378:metabolism; D051379:Mice; D019713:Receptors, CCR5; D013154:Spleen / Q000473:pathology / Q000821:virology; D018523:Tropism / Q000502:physiology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
C584933:CCR5 protein, human; D019713:Receptors, CCR5; D054299:env Gene Products, Human Immunodeficiency Virus