Rota Virus

Biology of rotavirus

Family = Reoviridae

Genus = Rotavirus

Introduction

• The most common cause of diarrheal diseases among infants and young children is due to rotavirus.
• Rotavirus was discovered in 1973 by Ruth Bishop.
• It belongs to the family Reoviridae and having double-stranded RNA viruses.
• Most of the child is infected with rotavirus at least once by the age of five. But with the occurrence of each infection, immunity is developed due to which subsequent infections becomes less severe.
• Adults are rarely affected by this rotavirus.
• A, B, C, D, E, F, and G are the eight different species of rotavirus based on the antigenicity and electrophoretic mobility of their RNA segments.
• Rotavirus A, the most common species, causes more than 90% of rotavirus infections in humans.
• The rotavirus is commonly transmitted from person to person by faecal-oral route.
• The lining of the small intestine is infected by this virus and causes gastroenteritis. It is often called as "stomach flu" though it has no relation to influenza.
• In addition to its impact on human health, rotavirus also tends to infect animals and is a pathogen of livestock.
• Rotavirus is usually an easily managed disease of childhood, but in 2013, rotavirus caused 215,000 deaths and 37 percent of deaths of children from diarrhoea, almost two million more become severely ill. The most of these deaths occurred in developing countries.

Structure

• It is non-enveloped with outer and inner capsid. It has a wheel-shaped appearance.
• It is double stranded RNA virus having 11 segments in the RNA.
• The capsid is composed of following proteins;

I Outer structure proteins: VP 7 and VP4.

ii The viral hemagglutinin and forms spikes from the surface.

iii Inner core structure proteins VP, VP2, VP3, and VP6 which are important antigenic determinants.

VP 4

VP 4 is protease cleaved or p protein. VP4 forms fine spikes on the outer of the capsid of the virus. It functions as hemagglutinin. It requires processing by host pancreatic protease in the GI tract to activate it. VP4 is the target of neutralizing antibody. This protein is used to determine the p serotypes of rotavirus.

VP 7

It is a glycoproteins or G proteins. It forms the shell of the outer capsid. It is also a target of neutralizing antibody. It is another protein used to determine the G serotype of the virus.

VP 6

It is the timers’ forms in the inner capsid. It is the most abundant viral proteins. Antibody to VP6 determines the group of rotavirus and is useful in diagnosis.

Types of rotavirus

• Among the seven different groups of rotavirus, referred to as A, B, C, D, E, F and G, humans strains of rotavirus that primarily infect are A, B, and C but most commonly by species A.
• Group A rotavirus is the most important pathogen. Group B causes an epidemic in China. Group C causes sporadic disease in children.
• Group D, E, A, and F have not been found in humans.
• VP 6 protein is the major determinant of group reactivity. This VP 6 protein has been used to subdivide group A rotavirus into subgroups I and II.
• A–E species cause disease in other animals.
• Rotavirus is classified into serotypes based on VP 7 and VP 4.
• There are 8 serotypes of rotavirus based on antibodies to VP 7 (G serotypes)
• There are 10 serotypes of rotavirus based on VP4 (P serotypes).
• The serotyping system of rotavirus uses a binary classification and references both the P type and G type.
• Worldwide, there are 4 strains predominant; p[8]G1, P[8]G3, P[8]G4 and p[4]G2.
• New serotypes such as G8[Asia] and G9[Africa] are emerging.

Transmission

• Transmission of rotavirus occurs through the fecal-oral route.
• The virus is stable in the environment and can be passed via fomites or contaminated food or water.

Pathogenesis

• Following infection, fever and abdominal cramps are common.
• RBCs or leukocytes are not found in the stool of patients.
• Morphology changes of the mucosa of small intestine occur. There are shortening and atrophy of the villi and mononuclear cell infiltration of the lamina proper.
• Virus invasion of epithelial cells of small intestine causes the destruction of mature absorptive cells and then replaced with young one's virus-free cells.
• Diarrhoea occurs due to:

i Immune replacement cells have reduced ability to absorb salt and water.

ii Immature cells have reduced ability to produce disaccharidases which result in malabsorption of carbohydrates.

iii Virus secrets a protein that functions as an enterotoxin and stimulates chloride and water secretion in the gut.

iv The enteric nervous system is activated.

• Chronic diarrhea and prolonged shedding have been associated with rotavirus infection in children with T- cell immunodeficiency.

Sign and symptoms

• Rotaviral enteritisis a mild to severe disease characterised by various symptoms such as nausea, vomiting, watery diarrhoea as well as low-grade fever.
• The incubation period is about two days before the appearance of symptoms. Once a child is infected by the virus, they undergo incubation period and finally lead to the period of illness which is acute.
• A low-grade fever may be present.
• Symptoms range from asymptomatic to severe.
• Symptoms often start with vomiting followed by four to eight days of profuse diarrhoea.
• In rotavirus infection, dehydration is more common and is the most common cause of death related to rotavirus infection.
• Rotavirus A infections can occur throughout both symptomatic and asymptomatic stage.Consequently, symptomatic infection rates are highest in children under two years of age and decrease progressively towards 45years of age

Epidemiology of rotavirus

• Rotaviruses are the most common cause of severe diarrhea in infants and children less than 3 years of age.
• 50-80% all cases of viral gastroenteritis are due to rotaviruses.
• It is usually endemic but responsible for occasional outbreaks.
• It causes infection in all age groups but most severe symptoms appear in a neonate and young children.
• Asymptomatic infections are common in people over 60 years of age.
• The mortality rate is up to 30% in malnourished children and responsible for up to half of million deaths per year.
• Seasonality: In temperature climate, rotavirus has a winter seasonal pattern. In a tropical climate, a disease caused by rotavirus occurs year around.
• Geography: Rotavirus occurs with equal frequency in underdeveloped and underdeveloped countries.
• Age: one-half of the population has been exposed to rotavirus by 6-12 months of age. By age 3 years, everyone has been infected once. Severe diarrhea after age 3 is rare but mild cases occur.

Diagnosis

1. Antigen detection in stool

The monoclonal antibodies to rotavirus antigen are available. Therefore, ELISA can be used for the detection of antigen in a stool sample. However, this can detect only group A rotavirus.

2. Electron microscopy

Electron microscopy also detects rotavirus and can be used to detect all group rotavirus.

3. Culture

Group A rotaviruses can be cultured in monkey kidney cells, MA104, CaCo-2 cells etc. But, successful isolation often requires series passage. The technique takes a longer time, are more expensive to perform and have lower sensitivity than antigen detection methods.

4. Nucleic acid detection

PCR-based assays have greater sensitivity than EM and antigen-based diagnostic approaches for all group rotaviruses. RT-PCR assay is commonly used.

5. Genotyping

Epidemiological studies use pattern of viral RNA migration using gel electrophoresis. Different genetic strains may circulate in a given community, which can be detected by electrophenotyping.

REFERENCE

M, Cheesbrough. Medical Laboratory Manual for Tropical Countries. Vol. 2. London: ELBS, 2007.

Tille, P. Diagnostic Microbiology. 13th. Elsevier, 2014.

D, Grenwood, Slack RCB and Peutherer J. Medical Microbiology. Dunclude Livingstone: ELBS, 2001.