Reoviridae

Rotavirus
- There are six species of rotavirus, referred to as A, B, C, D, E, and F

- Group A, B, and C rotaviruses have been found both in humans and

animals, and groups D, E, and F rotaviruses have been found only
in animals

- Rotavirus A, the most common species, causes more than 90% of

infections in humans (severe diarrhoeal disease in young)

- Group B and C rotaviruses include those viruses associated with

animal epidemics of severe diarrhoea primarily in adults in China

- Globally, it causes more than a half a million deaths each year in

children younger than 5 years of age
 virus structure

• The rotavirus genome is

segmented linear dsRNA
VP4
genome. Contains 11
segments coding for 12
proteins

• It is non enveloped,
icosahedral, with a triple
layered capsid and a wheel-
like structure.
.

• It about 80 nm in diameter.
The VP4 forms spikes on the outer
coat and attaches the virion to the
host cell, playing a key role in cell
penetration and virulence. VP4

VP4 is nonglycosilated outer capsid

protein and is also responsible for
rotaviral hemagglutinin activity

In the presence of trypsin (a protease

enzyme found in the gut), VP4 is
cleaved into VP5 and VP8 and
this cleavage results in
enhancement of viral infectivity
and virulence
Rotavirus’s VP7 protein, which
forms most of the outer
layer, is the main target for
the host’s protective VP4
antibodies.

VP7 and VP4 are involved in

immunity to infection.

The VP6 forms the middle

shell, or capsid, of the virion
and is the most antigenic
structure of the virion
proteins and can be used to
identify rotavirus species
 Mechanisms of rotavirus pathogenesis
- Rotaviruses cause a very common disease known as human infantile
gastroenteritis

- The incubation period is less than 48 hours with a sudden onset of vomiting, a
high frequency of dehydration and a mean duration of diarrhoea lasting 5–6
days

- Rotavirus can survive the acidic environment in stomach and alkaline

environment in intestine

- Rotavirus binds to sialic acid receptors via VP4 (HA) protein and enter cells by
endocytosis or by direct fusion

- Viral replication occur after adsorption to epithelial cells covering the vili of the
small inestne (enterocytes)

- Maximal shedding of the virus occur 2 to 5 days after the start of diarrhoea but
can occur without symptoms
- Rotavirus infection causes reduction in total small intestinal surface
area via the destruction of gut cells called enterocytes, leading to a
decrease in net fluid absorption

- Healthy enterocytes secrete lactase into the small intestine; milk

intolerance due to lactase deficiency is a symptom of rotavirus
infection which can persist for weeks

- Rotavirus infection prevents the absorption of water, causing a net

secretion of water and loss of ions, which together result in a watery
diarrhoea

- The NSP4 protein (NSP4 enterotoxin) of rotavirus act to promote

calcium ion influx into enterocytes, release of neuronal activators, and
a neuronal alteration in water absorption

- The loss of fluids and electrolytes can leads to sever dehydration and
even death
The sodium glucose cotransporter-1 (SGLT-1)
serotonin (5-HT)
Prostaglandin (PG)
vasoactive intestinal peptide (VIP)
 Immunity to rotavirus infection
• Rotavirus infection results in both serum
IgG and IgA and intestinal IgA responses

• The immunity to rotavirus infection VP4

requires the presence of IgA in the lumen
of the gut (IgA is highly prtective)

• VP4 ad VP7 induce neutralizing

anybodies (mainly IgA) that can block
enterocytes infection directly

• Actively or passively acquired antibody

(including antibody in colostrum and
mother’s milk, IgG and IgA) can lessen
the severity of disease but does not
consistently prevent reinfection
 Clinical signs and symptoms of rotavirus infection
Symptoms of Rotavirus Infection:

-It is asymptomatic in adults but it causes sever fatal disase in children

-Rotavirus is a virus that causes gastroenteritis (inflammation of the

stomach and intestines).

-Approximately two days following exposure to the virus, symptoms

typically begin with mild fever, upset stomach, abdominal pain, vomiting,
followed by watery diarrhea that lasts 3 to 8 days. Loss of fluids can be
accompanied with dehydration.

-The infection is usually self-limiting for healthy people, but in babies

and young children , it can lead to dehydration (loss of body fluids) which
may result in hospitalization or death.
 Transmission
• Rotavirus infections are more common between November and May,
coinciding with the time of year that children are in school and are more
likely to be in closer contact with other children.

• RV is transmitted directly from person to person by the fecal-oral route,

and via the respiratory route

• In addition, the virus is commonly transmitted in close communities,

such as daycare centers, nursing homes and within families

• The faeces of an infected person can contain more than 10 trillion

infectious particles per gram

• The virus survives well on fomites such as furniture and toys as well as
on hands and surfaces because it can withstand drying
Who’s at risk?
• Since rotavirus is very contagious, all people can get infected.

• Small children younger than 5 years of age

• In addition, people with weaker immune systems, such as the elderly

or HIV patients, are also more likely to have severe symptoms.

• Approximately 40% to 50% of hospitalizations for diarrhea are due

to rotavirus, and 20 to 60 deaths due to rotavirus occur each year in
the United States.

• In developing countries, rotavirus causes more than 500,000 deaths

each year in children less than 5 years of age.
Treatment of Rotavirus Infection:

-No specific antiviral therapy is available for a rotavirus infection

-The purpose of the therapy is to replace fluids (elctrolytes) and correct the
acid-base imbalances

-Since the infection itself is self-limiting, treatment for rotavirus infections

consists of oral rehydration therapy for individuals who are dehydrated
from severe loss of fluids from diarrhea.

-Oral rehydration therapy (ORT) consists of a mixture of water, sugar and

salts

-In severe cases of dehydration, an emergency room visit and/or

hospitalization may be necessary, during which an IV line is used for direct
rehydration
Rotavirus Prevention:
There are two newly licensed vaccines contain attenuated live virus to prevent
Rotavirus disease.
-Rotarix (GSK) and
-RotaTeq® (Merck and Co.)
Both have shown high rates of prevention and large reductions in hospitalizations
due to rotavirus

Recommended number of doses

Two or three doses before the age of 8 months.
Note: Unlike most vaccines, the rotavirus vaccine is given by mouth rather than
as an injection.

Recommended ages
-At 2 months
-At 4 months
-At 6 months (not needed if the Rotarix brand of vaccine was given at 2 and 4
months)
 Rotavirus vaccine program in UK

A new vaccination programme, planned to begin in September 2013, will see

children under 4 months vaccinated against the highly infectious rotavirus.

Causing around 140,000 diarrhoea cases a year in the under-5s, rotavirus leads to
hospital stays for nearly 1 in 10 (around 14,000) of those who get it in the UK.

The oral vaccine, which is expected to halve the number of vomiting and diarrhoea
cases caused by rotavirus and lead to 70% fewer hospital stays, will be given to
infants in 2 separate doses with other routine vaccines.

Rotavirus vaccines, including the Rotarix vaccine which will be used in the UK,
are already used to routinely vaccinate children in many countries including the
US, Nicaragua and Mexico (vaccine came into use in 2006).

Studies in the US have shown that rotavirus-related hospital admissions for young
children have been cut by more than two thirds since rotavirus vaccination was
introduced