Weak bases affect late stages of Mayaro virus replication cycle in vertebrate cells

Abstract

This paper describes the effect of two weak bases (ammonium chloride and chloroquine) on the morphogenesis of Mayaro virus. When Mayaro virus-infected TC7 (monkey kidney) cells were treated with these agents it was observed that weak bases caused a signi®cant reduction in virus yield. Also, cellular protein synthesis, which is inhibited by Mayaro virus infection, recovered to nearly normal levels. However, the synthesis of Mayaro virus proteins was affected. These phenomena were dose-dependent. The process of Mayaro virus infection in vertebrate cells is very rapid. Virus precursors are not observed in cell cytoplasm and budding through the plasma membrane seems to be the only way of virus release. Electron microscopy of cells infected with Mayaro virus and treated with weak bases revealed an accumulation of virus structures in cell cytoplasm. The study also noted an inhibition of budding through the plasma membrane and the appearance of virus particles inside intracytoplasmic vacuoles. These observations indicate an impairment at the ®nal stages of the virus replication cycle.

Rhesus Rhadinovirus Infection of Rhesus Fibroblasts Occurs through Clathrin-Mediated Endocytosis

“…Monensin, a sodium ionophore, binds monovalent cations, leading to an increase in endosomal pH (16). NH 4 Cl, an inhibitor of vacuolar acidification, is often used to examine pH sensitivity during virus entry (8). RFs were pretreated with different concentrations of the inhibitors for 1 h and were then infected with RRV-luciferase in the presence of the inhibitors.…”

Virus Mayaro: un arbovirus reemergente en Venezuela y Latinoamérica

“…El hecho de poseer ARN de material genético, le da a este virus una gran adaptabilidad debido a la alta tasa de mutaciones, lo que aumenta la probabilidad de adaptación a nuevos organismos, tanto vertebrados como invertebrados, que pueden servir de hospedadores (1,2,(15)(16)(17)(18)(19)(20)(21)(22).…”

“…El material genómico de los alfavirus, incluyendo al virus Mayaro, puede subdividirse en dos regiones: la subregión genómica, o región subgenómica 5´, que constituye dos tercios del genoma y codifica para proteínas no estructurales (nsP1, nsP2, nsP3 y nsP4), y la subregión subgenómica 3´, que representa un tercio del genoma y codifica para proteínas estructurales (E1, E2, E3, C, y 6K) (15)(16)(17)(18)(19)(20)(21). En la figura 1 se presenta de manera esquemática el genoma de los alfavirus.…”

“…El genoma de estos virus forma un complejo con la proteína del núcleo (proteína C), formando una nucleocápside icosaédrica (15)(16)(17)(18)(19)(20)(21). Las proteínas de envoltura celular que rodean la cápside, están formadas por restos de la membrana plasmática de células hospedadoras y por dos glucoproteínas, E1 y E2 (espículas); usualmente, la E3 se desprende de la mayoría de los alfavirus (15)(16)(17)(18)(19).…”

“…La glucoproteína E2 es responsable del contacto entre partículas virales y la superficie celular, ya que los anticuerpos anti-E2 pueden neutralizar la capacidad de infección viral, lo cual no se observa al emplear anticuerpos anti-E1 (2,(15)(16)(17)(18)(19)(20)(21). Una vez que la E2 interactúa con el receptor específico, el virus es introducido en una vesícula endocítica.…”