Table of Content:
- Introduction
- Structure of Human Astrovirus
- Genome of Human Astrovirus
- Transmission and Epidemiology
- Replication
- Pathogenesis
- Clinical Manifestation
- Diagnosis
- Treatment
- Prevention and Control
- Recent Development
- References
Introduction
Human Astrovirus (HAstV) is a significant viral pathogen belonging to the Astroviridae family and the Mamastrovirus genus. It is known to cause gastroenteritis, particularly in young children, the elderly, and immunocompromised individuals. The virus is highly stable in the environment and primarily transmitted through the fecal-oral route, contaminated food, and water.
Structure of Human Astrovirus
Human Astroviruses are small, non-enveloped, spherical viruses measuring approximately 28-35 nm in diameter. They exhibit an icosahedral symmetry and possess a single-stranded RNA (ssRNA) genome with positive polarity. The viral particles have a characteristic five- or six-pointed star-like surface pattern, which inspired the name "astrovirus" (Greek: astron - star). The surface appears rough, with small protruding spikes, and the virus has a buoyant density ranging between 1.35 and 1.37 g/ml in cesium chloride (CsCl).
Capsid Proteins and Maturation
The capsid precursor protein, consisting of 180 copies per viral particle, undergoes cleavage by host caspases during maturation. Infectious particles are produced by further proteolytic processing of the VP70 precursor protein by extracellular proteases, resulting in three structural proteins:
- VP34: Forms the capsid shell and is derived from the conserved N-terminal region.
- VP27 and VP25: Derived from the C-terminal domain, contributing to spike formation.
There are at least eight distinct serotypes of HAstV (HAstV-1 to HAstV-8), distinguished by genetic and antigenic variations.
Genome of Human Astrovirus
The HAstV genome is a linear, monopartite ssRNA(+) molecule, ranging between 6.8 and 7 kb in length. The 5′ terminus is linked to a viral protein genome-linked (VPg) protein, while the 3′ terminus features a poly(A) tail. The genome serves both as a genetic template and messenger RNA (mRNA) for viral protein synthesis.
Open Reading Frames (ORFs)
The genome consists of three overlapping Open Reading Frames (ORFs):
- ORF1a: Encodes nonstructural proteins, including viral proteases.
- ORF1b: Encodes the RNA-dependent RNA polymerase (RdRp), translated via ribosomal frameshifting.
- ORF2: Encodes the VP90 capsid precursor protein, expressed from a subgenomic RNA.
Transmission and Epidemiology
HAstV spreads predominantly through the fecal-oral route, person-to-person contact, and ingestion of contaminated food or water. Studies indicate the virus is highly stable in various environmental reservoirs, including drinking water, freshwater, and seawater. The virus exhibits a global distribution and disproportionately affects young children (1-3 years old), though outbreaks have been reported in adults, particularly in Japan.
Seasonal and Geographic Patterns
- HAstV infections peak in winter in temperate regions, similar to rotavirus.
- The virus is responsible for 4-8.6% of diarrheal cases in children, with variations based on geography.
- It has been linked to foodborne gastroenteritis outbreaks in adults and school children.
- Immunocompromised individuals, such as AIDS patients and organ transplant recipients, are at a higher risk of severe infection.
Replication Cycle
- Attachment and Entry: HAstV binds to host cell receptors and enters via endocytosis.
- Uncoating: The viral RNA is released into the cytoplasm.
- Translation and Polyprotein Processing:
- The genome is translated into two large polyproteins (nsP1a and nsP1a/1b).
- The viral protease and host cellular proteases process these polyproteins into functional nonstructural proteins.
- Genome Replication:
- A full-length negative-sense RNA template is synthesized.
- This template is used to generate new positive-sense genomic and subgenomic RNAs.
- Capsid Assembly and Maturation:
- The capsid precursor VP90 assembles into immature virions.
- VP90 is cleaved into VP70 by caspases.
- Trypsin further processes VP70 to enhance infectivity.
- Release: The virus exits the host cell via lysis or non-lytic mechanisms.
Pathogenesis
HAstV primarily targets intestinal epithelial cells, leading to:
- Destruction of enterocytes, disrupting absorption and secretion functions.
- Inhibition of epithelial permeability, contributing to diarrhea.
- Systemic spread in immunocompromised individuals, though rare.
Both humoral (IgA) and cellular (CD4+/CD8+ T cells) immune responses play a role in protection. The virus is excreted in high concentrations (up to 10¹³ genome copies/g) and can persist in stool for up to two weeks post-symptoms.
Clinical Manifestations
- Incubation period: 4-5 days.
- Symptoms: Watery diarrhea (lasting 1-4+ days), abdominal pain, fever, anorexia, and occasional vomiting.
- Severity: Milder than rotavirus; severe cases in malnourished children and immunocompromised patients.
- Shedding duration: 1-2 days pre-symptoms, 4-5 days post-recovery.
Diagnosis
- Electron Microscopy (EM): Direct detection in stool samples.
- Enzyme Immunoassay (EIA): Uses monoclonal antibodies for virus detection.
- Latex Agglutination Test: Specific for HAstV-1.
- ELISA and Immunofluorescence: Detects HAstV antibodies.
- Reverse Transcription-PCR (RT-PCR): Gold standard for genotyping and detection.
Treatment
There is no antiviral treatment available. Management includes:
- Oral or intravenous rehydration therapy to prevent dehydration.
- Supportive care to manage symptoms.
Prevention and Control
Currently, no vaccines exist against HAstV. Preventive measures focus on interrupting transmission routes:
- Hygiene Practices: Proper handwashing and sanitation.
- Food and Water Safety: Routine testing and decontamination.
- Disinfection: Use of appropriate disinfectants for contaminated surfaces.
Recent Developments
- Studies on HAstV variants: Emerging strains with altered pathogenicity and zoonotic potential are under investigation.
- Vaccine Research: Efforts are ongoing to develop an effective vaccine, focusing on capsid proteins.
- Environmental Surveillance: Detection of HAstV in wastewater suggests potential use as a marker for viral gastroenteritis outbreaks.
References
- Schultz-Cherry, S. Astrovirus Research: Essential Ideas, Everyday Impacts, Future Directions. Springer, New York, NY, USA, 2013.
- Viral Zone, Swiss Institute of Bioinformatics.
- Vu, D. L., Bosch, A., Pintó, R. M., & Guix, S. (2017). Human astrovirus epidemiology and pathogenesis in developing countries. Clinical Microbiology Reviews, 30(3), 541-565. doi: 10.1128/CMR.00013-14.
- Méndez, E., & Arias, C. F. (2013). Astroviruses. In Fields Virology (6th ed., pp. 609-632). Lippincott Williams & Wilkins.
