The Capsid Precursor Protein of Astrovirus VA1 Is Proteolytically Processed Intracellularly

Abstract

Human astrovirus VA1 has been associated with neurological disease in immunocompromised patients. Its recent propagation in cell culture has facilitated the study of its biology.

Attenuation hotspots in neurotropic human astroviruses

“…4C), the processing of MLB1 capsid is not sensitive to cellular caspase inhibitors (Fig. 4F), resembling another neurotropic astrovirus, VA1 29 . In contrast to neurotropic VA1 and MLB groups of astroviruses, the infectivity of classical astroviruses strongly depends on exogenous trypsin activation 2,29 .…”

“…4F), resembling another neurotropic astrovirus, VA1 29 . In contrast to neurotropic VA1 and MLB groups of astroviruses, the infectivity of classical astroviruses strongly depends on exogenous trypsin activation 2,29 . Since trypsin is a gut-specific enzyme, this may also explain the extra-gastrointestinal tract tropism of MLB astroviruses, including their ability to infect cell lines of different origins, such as Huh7 (hepatocarcinoma) and A549 (lung adenocarcinoma) 2 .…”

“…Despite the required function of caspases, the astrovirus release is described as an unclassified nonlytic process 8 . In some astroviruses, the structural polyprotein is cleaved by trypsin resulting in the formation of 3ʹ truncated (25)(26)(27)(28)(29)(30)(31)(32)(33)(34) proteins. Maturation of the astrovirus capsid protein is a very dynamic process, transforming the virus from a non-infectious intracellular form (VP90) to a primed extracellular form (VP70), and finally generating an icosahedral infectious mature virion (VP34/27/25).…”

Antigenic determinants of HAstV-VA1 neutralization and their relevance in the human immune response

“…In the case of the nonclassical VA1 strain, the capsid of the mature, infectious virion is composed of two polypeptides: VP33, which constitutes the shell of the virus particle (basic region and inner core structural domain), and VP38, which forms dimeric globular spikes that protrude from the virion (outer core and spike structural domains) (14). These two polypeptides are derived from a capsid precursor protein of 86 kDa (VP86) processed intracellularly by an undefined protease (14). Previously, the antigenic sites of neutralizing monoclonal antibodies (Nt-MAbs) to the capsid spike domain of classical HAstVs have been mapped (15)(16)(17).…”

“…HAstVs are small, nonenveloped viruses with a single-stranded, positive-sense RNA genome of approximately 6.7 kb (1, 2). In the case of the nonclassical VA1 strain, the capsid of the mature, infectious virion is composed of two polypeptides: VP33, which constitutes the shell of the virus particle (basic region and inner core structural domain), and VP38, which forms dimeric globular spikes that protrude from the virion (outer core and spike structural domains) (14). These two polypeptides are derived from a capsid precursor protein of 86 kDa (VP86) processed intracellularly by an undefined protease (14).…”