Phospholipid biosynthesis and poliovirus genome replication, two coupled phenomena.

Abstract

Poliovirus infection leads to an increase of phospholipid synthesis and the proliferation of new membranes, giving rise to a great number of cytoplasmic vesicles in the infected cells. Viral RNA replication is physically associated with these newly-synthesized membranes. Cerulenin, an inhibitor of lipid biosynthesis, effectively blocks the growth of poliovirus in HeLa cells. The presence of cerulenin after virus entry prevents the synthesis of poliovirus proteins. However, if this antibiotic is added at later stages of the virus replication cycle, it has no effect on viral translation itself, nor on the proteolytic processing and myristoylation of poliovirus proteins. The synthesis of viral, but not cellular RNA is selectively inhibited by cerulenin. Analysis of the viral RNA made in poliovirus-infected cells by specific minusor plus-stranded RNA probes suggests a selective blockade by cerulenin of plus-strand RNA synthesis. Finally, the synthesis of phospholipids and the proliferation of membranes does not take place if cerulenin is added to the culture medium. These findings indicate that continuous phospholipid synthesis is required for efficient poliovirus genome replication and provide new insights towards the understanding of the molecular events that occur during poliovirus growth.

Aurothiolates enhance the replication of Semliki Forest virus in the CNS and the exocrine pancreas

“…A 500-fold enhancement of coxsackievirus B3 titer in the pancreas of GSTM treated mice has previously been reported (Kabiri et al, 1978). Although picornaviruses are not enveloped, their replication is critically dependent on the availability of intracellular smooth membranes and on lipid biosynthesis (Guinea and Carrasco, 1990;Caliguiri and Tamm, 1970). The coxsackie virus data is therefore consistent with gold (I)-enhancement of virus replication operating through effects on intracellular membrane biochemistry.…”

Poliovirus 2Apro expression inhibits growth of yeast cells

“…Although specific poliovirus proteins participate in cytopathogenicity of the host cell during poliovirus growth, the mechanisms involved remain poorly understood. Such modification includes an increase in phospholipid synthesis [4], membrane proliferation [5], inhibition of host translation [6,7] and modification of membrane permeability [8 10]. Since all poliovirus proteins are synthesized in equal proportions throughout the virus life cycle it is difficult to assess which viral protein(s) is responsible for modifying a given cellular process.…”

Hepatitis C virus RNA replication is regulated by host geranylgeranylation and fatty acids

“…These data strongly suggest that HCV may directly affect one or more steps in cholesterol and͞or fatty acid biosynthesis. This is not surprising because cholesterol, fatty acids, and lipid rafts have been demonstrated to be critical for efficient replication and͞or infection of RNA and many DNA viruses (18)(19)(20)(21)(22)(23)(24)(25)(26)(27).Genes encoding enzymes involved in cholesterol and fatty acid biosynthesis are transcriptionally regulated by sterol regulatory element-binding proteins (SREBPs), which are members of a family of the basic helix-loop-helix leucine-zipper family of transcription factors (reviewed in ref. 28).…”