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Review
. 2021 Feb 4:12:631274.
doi: 10.3389/fmicb.2021.631274. eCollection 2021.

Membrane Rafts: Portals for Viral Entry

Inés Ripa  1   2 , Sabina Andreu  1   2 , José Antonio López-Guerrero  1   2 , Raquel Bello-Morales  1   2
Affiliations
Review

Membrane Rafts: Portals for Viral Entry

Inés Ripa et al. Front Microbiol. .

Abstract

Membrane rafts are dynamic, small (10-200 nm) domains enriched with cholesterol and sphingolipids that compartmentalize cellular processes. Rafts participate in roles essential to the lifecycle of different viral families including virus entry, assembly and/or budding events. Rafts seem to participate in virus attachment and recruitment to the cell surface, as well as the endocytic and non-endocytic mechanisms some viruses use to enter host cells. In this review, we will introduce the specific role of rafts in viral entry and define cellular factors implied in the choice of one entry pathway over the others. Finally, we will summarize the most relevant information about raft participation in the entry process of enveloped and non-enveloped viruses.

Keywords: caveolae; cholesterol; endocytosis; raft; viral entry.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Membrane raft structure. Lipid rafts are composed of cholesterol, saturated phospholipids and sphingolipids, such as glycolipids and sphingomyelin (SM). GPI-anchored proteins and lipidated – especially palmitoylated- proteins have a higher affinity for lipid rafts than non-lipid rafts.
FIGURE 2
FIGURE 2
(i) Simian virus 40 (SV40) entry by caveolae. SV40 binding to major histocompatibility class I (MHC-I) molecules targets the viral particles to lipid rafts, where multivalent binding to the ganglioside GM1 promotes viral entry by caveolae. Caveolae-mediated endocytosis can be exploited by other viruses, such as HCoC-229E, JEV or EV71. (ii) Adeno-associated virus type 2 (AAV2) entry by non-clathrin non-caveolae raft-dependent endocytosis. AAV2 enters the cells via clathrin-independent carrier/GPI-anchored protein early endosomal compartment (CLIC/GEEC). The formation of tubular vesicles by GRAF1-dependent endocytosis is mediated by the complementary roles of Cdc42 and Arf1 in regulating actin polymerization. Non-clathrin non-caveolae raft-dependent endocytosis can be also exploited by SV40 and SARS-CoV.
FIGURE 3
FIGURE 3
Kaposi’s sarcoma-associated herpesvirus (KSHV) entry by raft-dependent macropinocytosis in endothelial cells. Initial viral attachment occurs in non-lipid rafts. E3 ubiquitin ligase c-Cbl and membrane rafts determine the posterior location of receptors and the KSHV entry pathway. Polyubiquitination of the receptor αVβ5 leads to non-productive viral entry via clathrin in non-lipid rafts. Monoubiquitination of αVβ3 and α3β1 integrins induces the translocation of viral particles and receptors to lipid rafts, leading to productive viral entry via macropinocytosis. Viral entry by macropinocytosis in a raft-dependent manner has been also observed in EBOV infection.
FIGURE 4
FIGURE 4
Human immunodeficiency virus type 1 (HIV-1) entry by raft-dependent fusion in T lymphocytes. HIV-1 binds to CD4 receptor and CCR5 co-receptor within rafts. Interaction of CD4 with gp120 induces conformation changes which recruit the CXCR4 co-receptor to the periphery of the raft. Fusogenic activity of gp41 promotes fusion of the viral envelope and plasma membrane. The HIV-1 virulence factor Nef promotes budding of HIV-1 from membrane rafts, generating a viral progeny with a higher proportion of rafts in their envelopes and, thus, a higher infectivity. Viral entry by fusion in a raft-dependent manner has been also observed in EBOV, HSV-1, and MHV infections.
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