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Human Astroviruses Albert Bosch, Rosa M. Pintó and Susana Guix Clin. Microbiol. Rev. 2014, 27(4):1048. DOI: 10.1128/CMR.00013-14. Downloaded from Updated information and services can be found at: http://cmr.asm.org/content/27/4/1048 These include: http://cmr.asm.org/ REFERENCES This article cites 296 articles, 106 of which can be accessed free at: http://cmr.asm.org/content/27/4/1048#ref-list-1 CONTENT ALERTS Receive: RSS Feeds, eTOCs, free email alerts (when new articles cite this article), more» on October 2, 2014 by UNIVERSITAT DE BARCELONA Information about commercial reprint orders: http://journals.asm.org/site/misc/reprints.xhtml To subscribe to to another ASM Journal go to: http://journals.asm.org/site/subscriptions/ Human Astroviruses Albert Bosch, Rosa M. Pintó, Susana Guix Enteric Virus Laboratory, Department of Microbiology and Institute of Nutrition and Food Safety, University of Barcelona, Barcelona, Spain Downloaded from SUMMARY.................................................................................................................................................1048 INTRODUCTION ...........................................................................................................................................1048 BASIC VIROLOGY .........................................................................................................................................1049 Virion Structure and Assembly ..........................................................................................................................1049 Genome Organization ..................................................................................................................................1050 General Overview of the HAstV Replicative Cycle .......................................................................................................1051 Cell Binding and Entry ..................................................................................................................................1051 Translation/Replication .................................................................................................................................1051 Expression of Structural Proteins, Virion Assembly, and Cell Release....................................................................................1054 PATHOLOGY, PATHOGENESIS, AND HOST RESPONSE ..................................................................................................1054 http://cmr.asm.org/ Clinical Disease Correlates ..............................................................................................................................1054 Histopathological Changes .............................................................................................................................1055 Mechanisms of Pathogenesis and Induction of Diarrhea ...............................................................................................1056 Host Immune Responses and Control of Infection......................................................................................................1056 TAXONOMY, EVOLUTION, AND EMERGENCE ............................................................................................................1057 Human Astroviruses.....................................................................................................................................1059 Nonhuman Astroviruses ................................................................................................................................1060 EPIDEMIOLOGY ...........................................................................................................................................1060 HAstV Transmission .....................................................................................................................................1060 Age, Geographic, and Temporal Distribution ...........................................................................................................1061 Molecular Epidemiology of HAstV ......................................................................................................................1063 on October 2, 2014 by UNIVERSITAT DE BARCELONA LABORATORY DIAGNOSTICS .............................................................................................................................1063 Early Developments: Electron Microscopy and Immunological Assays .................................................................................1063 Molecular Assays ........................................................................................................................................1064 PREVENTION AND TREATMENT ..........................................................................................................................1065 CONCLUSIONS ............................................................................................................................................1065 ACKNOWLEDGMENTS ....................................................................................................................................1065 REFERENCES...............................................................................................................................................1065 AUTHOR BIOS .............................................................................................................................................1074 SUMMARY INTRODUCTION Human astroviruses (HAtVs) are positive-sense single-stranded sing electron microscopy (EM), Appleton and Higgins re- RNA viruses that were discovered in 1975. Astroviruses infecting Uported in 1975 the occurrence of 28- to 30-nm particles in other species, particularly mammalian and avian, were identified stools of children suffering from vomiting and mild diarrhea (1). and classified into the genera Mamastrovirus and Avastrovirus. The same year, Madeley and Cosgrove used the term astrovirus Through next-generation sequencing, many new astroviruses in- (AstV) to describe the small round viruses with a characteristic fecting different species, including humans, have been described, star-like appearance (“astron” means star in Greek) found in the and the Astroviridae family shows a high diversity and zoonotic feces of hospitalized infants with gastroenteritis (2). These parti- potential. Three divergent groups of HAstVs are recognized: the cles were placed together with other viruses with a smooth entire classic (MAstV 1), HAstV-MLB (MAstV 6), and HAstV-VA/HMO edge within the category of “small round viruses” (SRVs), which (MAstV 8 and MAstV 9) groups. Classic HAstVs contain 8 sero- differed from the “small round structured viruses” (SRSVs) that types and account for 2 to 9% of all acute nonbacterial gastroen- grouped particles with a rough, hairy, or irregular edge, such as teritis in children worldwide. Infections are usually self-limiting caliciviruses (3). but can also spread systemically and cause severe infections in The genomic and subgenomic organization of AstV and its immunocompromised patients. The other groups have also been polyprotein processing led to the proposal of the new family As- identified in children with gastroenteritis, but extraintestinal pa- troviridae, separated from the families Picornaviridae and Calici- thologies have been suggested for them as well. Classic HAstVs viridae, within the positive-sense single-stranded RNA (ssRNA) may be grown in cells, allowing the study of their cell cycle, which viruses (4). In 1995, the International Committee for the Taxon- is similar to that of caliciviruses. The continuous emergence of new astroviruses with a potential zoonotic transmission highlights the need to gain insights on their biology in order to prevent future Address correspondence to Albert Bosch, [email protected]. health threats. This review focuses on the basic virology, patho- Copyright © 2014, American Society for Microbiology. All Rights Reserved. genesis, host response, epidemiology, diagnostic assays, and pre- doi:10.1128/CMR.00013-14 vention strategies for HAstVs. 1048 cmr.asm.org Clinical Microbiology Reviews p. 1048–1074 October 2014 Volume 27 Number 4 Human Astroviruses TABLE 1 Main characteristics of the Astroviridae family BASIC VIROLOGY Characteristic Virion Structure and Assembly Virion structure The AstV virion is an icosahedral nonenveloped particle with a Icosahedral particles, 28–41 nm in diam smooth margin and a distinctive five- or six-pointed star identi- Nonenveloped fied on the surface of some (around 10%) virions (Fig. 1). Particles Distinctive five- or six-pointed star-like shape under the electron are assembled from the VP90 precursor protein (approximately microscope in about 10% of the virions 90 kDa), which is further processed by cellular caspases to gener- Genome ate the VP70 protein, losing an acidic C-terminal domain (37). Downloaded from A single molecule of infectious, positive-sense ssRNA, 6.4–7.7 kb, with a Particles composed of the 70-kDa protein are immature and re- poly(A) tail quire trypsin cleavages, which occur extracellularly through a Three ORFs: ORF1a and ORF1b at the 5= end encoding the nonstructural rather complicated pathway producing highly infectious particles proteins and ORF2 at the 3= end encoding the structural proteins with capsid proteins of 32 to 34, 27 to 29, and 25 to 26 kDa (VP34, VPg protein linked to the 5= end VP27/29, and VP25/26) (38). VP34 is derived from the highly A ribosomal frameshifting signal present
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