In Vivo HIV-1 Cell-to-Cell Transmission Promotes Multicopy Micro-compartmentalized Infection

• Published in: Cell reports (Cambridge) Vol. 15; no. 12; pp. 2771 - 2783
• Main Authors: Law, Kenneth M., Komarova, Natalia L., Yewdall, Alice W., Lee, Rebecca K., Herrera, Olga L., Wodarz, Dominik, Chen, Benjamin K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.06.2016; Elsevier
• Subjects: Animals; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; Cell Movement; Cell-Free System; Cells, Cultured; env Gene Products, Human Immunodeficiency Virus - metabolism; Gene Dosage; HIV Infections - blood; HIV Infections - virology; HIV-1 - physiology; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Immunological Synapses - metabolism; Lentivirus; Mice; Receptors, CCR5; Spleen - pathology; Spleen - virology; Tropism - physiology
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2016.05.059

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. [Display omitted] •Infected T cells co-transmit multiple HIV-1 copies to T cells in immune tissues•HIV-infected cells can migrate but frequently become anchored within tissues•Clustering of infected cells with the same genotype indicates local viral spread•HIV-1-infected cells slow the migration of uninfected T cells that contact them The role that cell-to-cell infection plays during HIV-1 spread within lymphoid tissues has been poorly defined. Law et al. find that HIV-infected T cells can form durable cell-cell contacts with other T cells in vivo, leading to clusters of infection that frequently co-transmit multiple viruses per cell.