Human immunodeficiency virus transmission—Mechanisms underlying the cell‐to‐cell spread of human immunodeficiency virus

Abstract

Despite the success of combined antiretroviral therapy in controlling viral load and reducing the risk of human immunodeficiency virus (HIV) transmission, an estimated 1.5 million new infections occurred worldwide in 2021. These new infections are mainly the result of sexual intercourse and thus involve cells present on the genital mucosa, such as dendritic cells (DCs), macrophages (Mø) and CD4+ T lymphocytes. Understanding the mechanisms by which HIV interacts with these cells and how HIV exploits these interactions to establish infection in a new human host is critical to the development of strategies to prevent and control HIV transmission. In this review, we explore how HIV has evolved to manipulate some of the physiological roles of these cells, thereby gaining access to strategic cellular niches that are critical for the spread and pathogenesis of HIV infection. The interaction of HIV with DCs, Mø and CD4+ T lymphocytes, and the role of the intercellular transfer of viral particles through the establishment of the infectious or virological synapses, but also through membrane protrusions such as filopodia and tunnelling nanotubes (TNTs), and cell fusion or cell engulfment processes are presented and discussed.

CD4+ T cells facilitate replication of primary HIV-1 strains in macrophages and formation of macrophage internal virus-containing compartments

“…However, their replication is readily detectable in CD4+ T cells (21,35,41). This block in macrophage infection can be overcome by cell-to-cell spread, where HIV-1 is directly transferred from macrophages to CD4+ T cells (16,17,35,(53)(54)(55)(56).…”

“…However, their replication is readily detectable in CD4+ T cells (21,35,41). This block in macrophage infection can be overcome by cell-to-cell spread, where HIV-1 is directly transferred from macrophages to CD4+ T cells (16,17,35,(53)(54)(55)(56). In addition, through processes like trans-cytosis, antigen-presenting cells including macrophages and DCs capture infectious virus to pass it on for CD4+ T cell infection (57).…”

“…cell contacts as for instance the immunological synapse or indirectly by secretion of cytokines and chemokines. Overall, such non-virus specific interactions seem to promote virus replication and spread (34,35). Furthermore, there is evidence for cytokine and chemokine secretion that might be both, beneficial as well as inhibitory in the context of virus replication (36)(37)(38)(39).…”

Beyond Impairment of Virion Infectivity: New Activities of the Anti-HIV Host Cell Factor SERINC5

“…Moreover, S5 activities have, so far, been exclusively studied in the context of infections with cell-free viruses. Since cell-associated modes of virus transmission play an important role in HIV-1 spread and provide a means to circumvent some host cell restrictions [ 94 , 95 , 96 , 97 ], it will be important to address the impact of S5 in the context of cell–cell transmission. Finally, a main challenge lies in the visualization of the S5 protein and the characterization of its function in a physiological context.…”