Intercellular HIV-1 transfer overcomes blockade of viral entry into macrophages

Understanding how HIV-1 hijacks immune cell functions to promote viral spread remains a challenge in the fight against infection. Macrophages are ubiquitous tissue cells involved in tissue homeostasis and immunity. In HIV-1 infection, macrophages along with CD4+ T lymphocytes serve as vectors for virus spread and persistent viral tissue reservoirs, presenting an obstacle to HIV-1 eradication. However, the mechanisms involved in macrophage infection remain incompletely understood. A paradox is that infected macrophages are present in a variety of tissues while cell tropism assays have been performed in vitro point out that only a limited number of HIV-1 isolates can enter macrophages.

Scientists have speculated that these tests, which assess infection using free viral particles, may not fully reflect macrophage infection patterns. live in infected patients. They show that intercellular virus transfer through intercellular fusion with infected CD4+ T cells is a highly efficient means of infecting macrophages, even with virus isolates that have been characterized as nontropic for macrophages in virus infection assays. This intercellular viral transfer is facilitated by enhanced interactions between HIV-1 envelope glycoproteins and the cellular entry receptors CD4 and the chemokine receptors CCR5 and CXCR4. This is what these results indicate HIV-1 has a much broader tropism for macrophages than originally thought.

These results underscore the role of this pathway of cell-to-cell viral delivery on macrophages in tissues rich in CD4+ T cells for the transmission, dissemination and formation of tissue viral reservoirs of HIV-1. The scientists propose that the infection of macrophages by intracellular virus transfer could affect various aspects of the pathophysiology of HIV-1 infection, renewing our understanding of the role of macrophages in HIV-1 pathogenesis and persistence.

© Serge Benichou

Figure: Model of intercellular transfer and spread of HIV-1 to macrophages of infected CD4+ T cells. Initial viral transfer and subsequent viral spread within macrophages is mediated by a two-step cell fusion process. First, the infected T cells make contact and then fuse with the macrophage targets (pink in the figure). The newly formed infected cells then acquire the ability to fuse with surrounding, uninfected macrophages, resulting in the formation of multinucleated giant cells capable of producing large quantities of infectious virus.

Learn more:
Cell-to-cell spread of HIV-1 overcomes viral entry blockade from non-macrophage-tropic strains into macrophages.
Han M, Cantaloube-Ferrieu V, Xie M, Armani-Tourret M, Woottum M, Pagès JC, et al.
PLoS pathogens 18(5): e1010335. https://doi.org/10.1371/journal.ppat.1010335

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