In Vivo HIV-1 Cell-to-Cell Transmission Promotes Multicopy Micro-compartmentalized Infection
Open accessAbstract
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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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.”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [129]
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].”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [129]
Cites
Rudnicka, D., Feldmann, J., Porrot, F., Wietgrefe, S., Guadagnini, S., Prévost, M.-C., Estaquier, J., Haase, A. T., Sol-Foulon, N., & Schwartz, O. (2009) · Journal of Virology · doi:10.1128/jvi.00282-09 · Cited by 229 · see citing works
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HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread
Kalinichenko, S., Komkov, D., & Mazurov, D. (2022) · Viruses · doi:10.3390/v14010152 · Cited by 68 · see citing works
“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…”
Background
- 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
- gold
- doi.org
- Licence
- 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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