Role of Lipid Transfer Proteins (LTPs) in the Viral Life Cycle

Abstract

Viruses are obligate parasites that depend on the host cell machinery for their replication and dissemination. Cellular lipids play a central role in multiple stages of the viral life cycle such as entry, replication, morphogenesis, and egress. Most viruses reorganize the host cell membranes for the establishment of viral replication complex. These specialized structures allow the segregation of replicating viral RNA from ribosomes and protect it from host nucleases. They also facilitate localized enrichment of cellular components required for viral replication and assembly. The specific composition of the lipid membrane governs its ability to form negative or positive curvature and possess a rigid or flexible form, which is crucial for membrane rearrangement and establishment of viral replication complexes. In this review, we highlight how different viruses manipulate host lipid transfer proteins and harness their functions to enrich different membrane compartments with specific lipids in order to facilitate multiple aspects of the viral life cycle.

Reovirus infection is regulated by NPC1 and endosomal cholesterol homeostasis

“…Based on the function of NPC1 in cell entry and replication of other viruses [ 39 ] and its identification in both CRISPR and siRNA screens, we evaluated a potential role for NPC1 in reovirus replication. HBMECs are susceptible to reovirus infection [ 40 ] and amenable to CRISPR/Cas-9 gene editing [ 41 ].…”

Coordination of inter-organelle communication and lipid fluxes by OSBP-related proteins

“…Importantly, increasing evidence points at functions of ORPs as host factors with key roles in the life cycles of pathogenic viruses and bacteria [228][229][230], making them candidate targets for new antiviral or -bacterial drugs. The same holds true for cancers: With an increasing number of reports on functions of ORPs in the survival and malignant proliferation of cancer cells [174,175,208,213,219,[284][285][286], one can envision ORPs as potential targets for future anticancer therapies.…”

“…Therefore, viruses modify host cell lipid metabolism, trafficking and signalling to create conditions optimally supporting the viral life cycle. Here, they exploit the cellular lipid transfer proteins including a number of the ORP family members [228]. Analogously, also bacterial pathogens can make use of the ORP machinery to secure their intracellular survival and proliferation, as shown for Salmonella [229,230].…”

Molecular mechanisms of PI4K regulation and their involvement in viral replication

“…The generation of ROs requires rewiring of lipid metabolism, concentration of different lipid species and manipulation of lipid transport. 20,22,108,109 Evidence in enteroviruses suggests that the origin of the RO is originally derived from the ER, with later ROs being derived from the TGN. 110 ROs make extensive contacts with both the ER and lipid droplets, with these contacts being critical in allowing for transport of lipids required for viral replication.…”

“…This involves the formation of double‐membrane vesicles, frequently referred to as ROs or the membranous web (Figure 4A,B). The generation of ROs requires rewiring of lipid metabolism, concentration of different lipid species and manipulation of lipid transport 20,22,108,109 . Evidence in enteroviruses suggests that the origin of the RO is originally derived from the ER, with later ROs being derived from the TGN 110 .…”