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Human Astro viruses

Presenter: M. S. Rahman
Moderator: Dr. Varsha A. Singh

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Introduction

Acute diarrhea (AD) - Two billion cases in children

per year worldwide

Human astro virus (HAstV) third ,after rotavirus group A


(RVA) and noro virus (NoV)

Recently novel astro virus strains isolated from humans have


been associated with diseases other than gastroenteritis.
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History
1975- First identified by Appleton, Higgins,
Madeley and Cosgrove
1982- Caul and Appleton visualized astrovirus
using appropriate immunological reagents
Eight traditional serotypes have been identified
in humans

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Epidemiology
Under 5 years old -9.9% of the 6.9 million
deaths (2011)
Mexico City- 365 diarrhoea episodes among 214
children (18 months old)
Brazil- 43 cases in 2004.
UK - in a primary immunodeficiency unit at
Newcastle General Hospital
China- 335 infants with diarrhoea in Wuhan
Spain- 4.9 % in children.
Korea -10,603 stool samples ( 2004 to 2008) 1.8 %

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Novosibirsk- 64 (5.8 %) January to December


2007
In Hungary- 4.27.3 % cases
France-1.5 % cases of children hospitalized
Saudi Arabia- 1.5 % of pediatric population
In India- Astrovirus infections was reported from
Kolkata
Classical serotypes 18 and three novel
astroviruses [AstV-VA2, AstV-VA3, and AstVMLB2] have been detected in Vellore

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Classification

Family- Astroviridae
Two genera-

1.Mamoastrovirus(MAstVs)
2.Avastrovirus(AAstVs)

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Mamalian Ast V
Include

Bovine AstV
Feline AStV
Human
AstV(Genotype 1-8)
Ovine AstV
Mink AstV
Porcine AstV

Avian Astrovirus
include

Duck AstV1
Turky Astv1 &2
Avian Nephritis
Virus(ANV)

Classification based on
the host of origin
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Structure of astro virus


Single-stranded, positive-sense RNA
Nonenveloped
Size- 2830 nm in diameter
Shape-small, round
Rough, hairy, irregular edge, smooth margin
Distinctive five- or six-pointed star-like appearance
(astron means star in Greek)
Symmetry-T=3 icosahedral symmetry studded with
globular dimeric spikes
30 vertices

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Structure of astro virus

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Capsid

Multidomain protein

Conserved N-terminal Region


Basic
Domain

S Domain

P1 Domain
P2 Domain

Viral genome and Capsid


Shell

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Highly variable C-terminal


Region

Spikes

Acidic
Domain

Genome Structure

Linear, Single-stranded, positive-sense RNA


5-terminus is linked to a VPg proteinActs as a primer during RNA synthesis
3-terminus has a poly(A) tractNuclear export, translation and stability of mRNA

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Viral Genome

ORF1a

Viral nonstructural
proteins & VPg

ORF1b

RNA-dependent
RNA polymerase

ORF2

Capsid
protein

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Mode of Transmission
Fecaloral route
Person-to-person contact.
Vomit and environmental surfaces (such as
hand-mouth contact)
Consumption of shellfish (faecally
contaminated)

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Viral replication and Pathogenesis


Attachment of Virus to Enterocytes
Endocytosis to host cell
Uncoating and release of RNA into the cytoplasm
Translation
Replication proteins
Replication
dsRNA genome(ER)
Transcription
mRNAs/new ssRNA(+) genomes
Translation
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Capsid protein precursor

Assembly of new virus

C1q/MBL

Inhibits complement activation

Maturation by host extracellular proteases


Cell destruction and release of Virus

Maladsorption of fluids and electrolytes


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Seasonal Variation

Winter season in temperate regions

Rainy season in tropical regions

Developing countries - poor sanitation

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Sign and symptoms


Last between 2 and 4 days
GIT- watery diarrhoea, vomiting,
abdominal pains
Others- Headache, fever, anorexia

Immunocompromised and elderly significant disease

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Lab Diagnosis
Sample: Feaces
Electron microscopy
Enzyme immunoassays
Astrovirus Capsid ELISA
Reverse transcription-polymerase chain
reaction (RT-PCR)
Nucleic acid dot-blot hybridization test
One step test

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One step test

For the qualitative detection of Astrovirus antigens

The membrane pre-coated with monoclonal antibodies against


Astrovirus antigens on the test line region

sample reacts with the particle coated with anti-Astrovirus


antibodies pre-dried on the test strip

Generate a coloured line


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Lab diagnosis

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Host Immune Responses


Humoral immune response IgA antibodies
Healthy young adults- most prevalent classic HAstV
serotypes
Maternal-fetal transmission upto 6 to 8 months
Indirect evidence

Small intestinal biopsy+ inactivated HAstVs


Culture
HAstV-specific CD4 and CD8 T cells

Prevention and treatment


Control measures:
Removal of common source of infection
(e.g., ill food handler or contamination of a
water supply)
Interruption of person-to-person
transmission.
Treatment : Patients may require fluid
replacement.
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NO VACCINE
In the future, immunization may play an
important role for preventing HAstV
infections.

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Thank You
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