Lipid Tales of Viral Replication and Transmission

Abstract

Positive strand RNA viruses are the largest group of RNA viruses on the planet and include many human, animal and plant pathogens. Cellular membranes are key players in all aspects of their life cycle, from entry and replication to assembly and exit. In particular, membranes are virally harnessed to serve as platforms for replication and as carriers to transmit viruses to other cells either as the envelope of a single virus or as the vesicle transporting a population of viruses. Studies have revealed significant convergence among different viruses to utilize membranes with specific lipid blueprints for replication and transmission. For replication many animal/human viruses utilize membranes enriched phosphatidylinositol 4-phosphate/cholesterol whereas many plant and insect-vectored animal viruses exploit ones with phosphatidylethanolamine/cholesterol. For transmission, phosphatidylserine enriched membranes are widely used as carriers for RNA and DNA viruses. Here we discuss the role of these membranes for viral pathogenesis and therapeutic development.

Long distance RNA movement

“…Most, if not all, mammalian and plant single‐stranded RNA viruses use host membranes as platforms for replication and as carriers to transmit these viruses to other cells (Altan‐Bonnet, ). Either they use membranes as an envelope or vesicles containing a population of viruses.…”

“…Either they use membranes as an envelope or vesicles containing a population of viruses. Notably, many plant, animal and human viruses appear to exploit phosphatidylinositol 4‐phosphate/cholesterol‐enriched membranes for replication and phosphatidylserine‐enriched membrane carriers are widely used for transmission (Altan‐Bonnet, ). In plants, replication complexes of BMV, rubella virus and tomato bushy stunt virus (TBSV) use the plasma membrane, the outer membrane of mitochondria, and peroxisomal membranes, respectively.…”

Phosphatidylserine Is the Signal for TAM Receptors and Their Ligands

“…When HIV, vaccinia, West Nile, Zika, and other viruses bud from virus-producing cells, their membrane envelopes can display significant levels of externalized PtdSer [84]. If these virus particles are exposed to environments containing TAM ligands – for example, if they pass through the blood where Pros1 is present at ~300 nM – they will effectively be opsonized with these ligands, to a greater or lesser extent as a function of the fraction of the virus surface that is exposed PtdSer.…”

Perception of double‐stranded RNA in plant antiviral immunity

“…TMV replication complexes associate with the ER and microtubules at cortical sites that may present direct contact with the plasma membrane (PM) and PM‐located proteins (Niehl et al ., ; Peña and Heinlein, ; Pitzalis and Heinlein, ), thus presenting a possibility for interaction between intracellularly produced viral dsRNA replication intermediates and membrane‐localized receptors. Typically, plant virus replication on membranes induces strong membrane modifications and is associated with interference of virus infection with lipid metabolism and membrane targeting and transport (Altan‐Bonnet, ; De Castro et al , ; Nagy, ; Nagy and Pogany, ; Zhang et al ., , ). Infection by diverse plant viruses has been shown to imply membrane fusion processes (Garcia Cabanillas et al ., ; Huang et al ., ; Wei et al ., ) as well as conventional and unconventional protein transport routes (Diaz et al ., ; Grangeon et al ., ; Kovalev et al ., ; Movahed et al ., ; Ribeiro et al ., ; Wang et al ., ; Wei and Wang, ).…”