Coxsackievirus B transmission and possible new roles for extracellular vesicles

Abstract

Coxsackievirus B1, a member of the Picornaviridae family is a non-enveloped single-stranded RNA virus associated with human diseases including myocarditis and pancreatitis. Infection of the intestinal mucosa, lined by polarized epithelial cells, requires interaction of coxsackievirus with apically located DAF (decay-accelerating factor) before transport to the basolaterally located CAR (coxsackie and adenovirus receptor), where entry is mediated by endocytosis. As with many other non-enveloped viruses, coxsackievirus has to induce lysis of host cells in order to perpetuate infection. However, recent evidence indicates that virus spread to secondary sites is not only achieved by a lytic mechanism and a non-lytic cell-cell strategy has been suggested for coxsackievirus B3. A physical interaction between infected and non-infected cells has been shown to be an efficient mechanism for retroviral transmission and one type of extracellular vesicle, the exosome, has been implicated in HIV-1 transmission. HIV-1 also takes advantage of depolymerization of actin for spread between T-cells. Calpain-mediated depolymerization of the actin cytoskeleton, as a result of increases in intracellular calcium concentration during coxsackievirus infection, would result in a release of host cell-derived microvesicles. If so, we speculate that maybe such microvesicles, increasingly recognized as major vehicles mediating intercellular communication, could play a role in the intercellular transmission of non-enveloped viruses.

Infectious bronchitis virus entry mainly depends on clathrin mediated endocytosis and requires classical endosomal/lysosomal system

“…Macropinocytosis is morphologically defined by the presence of membranous extensions of outwardly polymerizing actin termed membrane ruffles. It has been identified as an entry mechanism for several pathogens, including B2 adenovirus (Kalin et al, 2010), Coxsackie B virus (Inal and Jorfi, 2013), influenza A virus (de Vries et al, 2011), Ebola virus (Aleksandrowicz et al, 2011), Vaccinia virus (Rizopoulos et al, 2015), Nipah virus (Vogt et al, 2005), Kaposi's Sarcoma-Associated Herpesvirus (Raghu et al, 2009), and Newcastle disease virus (Tan et al, 2016).…”

Recent progress in understanding coxsackievirus replication, dissemination, and pathogenesis

“…Because exit via EMVs provide a non-cytolytic method for CVB escape, this mechanism could potentially prolong viral replication in the host cell. EMVs could also enhance viral stability in the extracellular space as well as mask the virus from host neutralizing antibodies (Inal & Jorfi, 2013) (Masciopinto, Giovani et al, 2004). Though intact virions were observed in EMVs observed under electron microscopy (Robinson, Tsueng et al, 2014), these structures could presumably contain free viral RNA and still remain infectious.…”

Vesicular Transport of Progeny Parvovirus Particles through ER and Golgi Regulates Maturation and Cytolysis

“…For instance SV40 was detected in intra-cytoplasmic smooth membrane vesicles and described as being released from the cell before cytopathic effects are seen [18]. Similarly, cocksackie B3 virus was found to be transferred from cell to cell through microvesicles [19]. We also recently reported that in the case of non-enveloped lytic parvoviruses that progeny virions are actively transported from the nucleus to the plasma membrane (PM) through vesicles in a gelsolin-dependent manner [20].…”