Alvarez et al.
Dec 18, 2014
This review focuses on the unique features of HIV-1 transmission through virological synapses (VS), which are specialized structures formed between infected and uninfected T cells.
This review focuses on the unique features of HIV-1 transmission through virological synapses (VS), which are specialized structures formed between infected and uninfected T cells. The paper highlights several key differences between cell-to-cell HIV transmission via VS and cell-free virus spread.
Key findings:
Cell-Cell Adhesion and Virus Assembly: The formation of a stable adhesion between infected and uninfected T cells initiates virus assembly at the VS, with viral proteins Gag and Env recruited to the contact site. This adhesion activates the virus assembly process, essential for efficient transmission.
Regulation of Membrane Fusion: Unlike cell-free virus, which activates Env-mediated fusion upon encountering CD4+ receptors, VS-mediated transmission involves a regulated fusion process. Fusion is delayed by interactions between viral proteins and host cell factors, ensuring that virus particles mature before fusion.
Neutralization Resistance: HIV-1 transmission through VS is more resistant to neutralizing antibodies than cell-free virus infection. The Env protein’s conformation is altered at the VS, making it less susceptible to neutralization.
Multicopy Infection and Drug Resistance: Cell-to-cell transmission leads to higher numbers of virus particles being transferred simultaneously, which can contribute to drug resistance by promoting multicopy infection. This increases the virus's ability to evade antiretroviral drugs.
Migration and Interaction: HIV-1 spread through VS is dependent on the migration of infected T cells. This process may contribute to the spatial distribution and systemic spread of HIV, emphasizing the role of cell migration in viral dissemination.
In conclusion, HIV-1 spread through T cell VS is a complex and highly efficient process that differs significantly from traditional cell-free infection. Understanding these mechanisms provides insights into how HIV evades immune responses and persists despite treatment.
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004513