Cited by 101HIV Research and TreatmentHIV/AIDS Research and InterventionsT-cell and Retrovirus Studies

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

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Law, Kenneth M., Komarova, Natalia L., Yewdall, Alice W., Lee, Rebecca K., Herrera, Olga L., Wodarz, Dominik, Chen, Benjamin K.·2016·Cell Reports

Abstract

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.

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Crossref · 10.1016/j.celrep.2016.05.059

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  • Cell-to-cell infection enhances co-transmission of two different strains of HIV-1 in vitro and in vivo; cell-cell contact can increase multiplicity of infection and diversity of HIV.

    “Law et al. have shown that cell-to-cell infection enhances co-transmission of two different strains of HIV-1 in vitro and in vivo [129]. This is well consistent with our results obtained using cell lines and two reporter vectors, inGFPt and in-mCherry [131], suggesting that cell-cell contact can increase multiplicity of infection and diversity of HIV.”
  • HIV-infected T cells in humanized mice circulate and migrate to lymph nodes and spleen, interact with uninfected cells, arrest motility to establish contact-dependent transfer, then move apart forming long tethering membrane protrusions.

    “Studies in humanized mice demonstrate that HIV-infected T cells retain the ability to circulate and migrate to the lymph nodes and spleen, where they can interact with uninfected cells, arrest their motility to establish contact-dependent transfer of HIV, and then move apart from each other with the formation of long tethering membrane protrusions [109,129].”

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Authors
Law, K. M., Komarova, N. L., Yewdall, A. W., Lee, R. K., Herrera, O. L., Wodarz, D., & Chen, B. K.
Affiliations
  • Icahn School of Medicine at Mount Sinai (US)
  • University of California, Irvine (US)
  • Mount Sinai Hospital (US)
Corresponding author
Chen, Benjamin K.
Venue
Cell Reports
Publisher
Elsevier BV
Published
2016-06
Volume
15
Issue
12
Pages
2771-2783
ISSN
2211-1247 (ISSN-L)
OpenAlex
W2412450517
Cited by
101
References
1
Citations by year
2026: 5 · 2025: 7 · 2024: 4 · 2023: 6 · 2022: 10 · 2021: 12 · 2020: 14 · 2019: 14 · 2018: 19 · 2017: 7 · 2016: 3
FWCI
9.93
Type
journal article
Language
en
Open access
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institutes of Health
  • National Institute on Drug Abuse (F31DA036425)
  • National Institute of General Medical Sciences
  • National Institute of Allergy and Infectious Diseases (R01AI093998, R01AI074420)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
Keywords
HIV-1, cell-to-cell transmission, virological synapse, co-transmission, humanized mice, viral genotypes, CD4+ T cells, intravital imaging, lymphoid tissue, antiretroviral resistance, viral spread
MeSH terms
Animals, Cell Movement, Cell-Free System, Cells, Cultured, Humans, Spleen, CD4-Positive T-Lymphocytes, HIV-1, HIV Infections, Tropism, Gene Dosage, Receptors, CCR5, Mice, env Gene Products, Human Immunodeficiency Virus, Immunological Synapses

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