Kapoor, Sanjay (1995) Molecular determinants of rotavirus virulence. PhD thesis, University of Warwick.

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Abstract

Rotaviruses are the single most important etiological agent of
severe diarrhoea in infants and young children in both developed and
developing countries. The World Health Organisation has identified the
development of a rotavirus vaccine as a priority area for routine
childhood immunisation to control rotavirus infections. However, the
candidate vaccine strains have not been very successful. The main aim of
this project was to map rotavirus virulence to its gene segments. Such
studies can help in developing better vaccines for the control of rotavirus
induced diarrhoea.
A three step approach was undertaken (i) development of an
animal model, (ii) construction and characterisation of reassortants
between rotavirus strains of different virulence, (iii) mapping virulence to
rotavirus gene segments.
The mouse model developed revealed that the outcome of rotavirus
infection was influenced by viral dose and viral strain as well as by host
age and host strain. Homologous murine rotavirus strain was found to be
most virulent. Among the heterologous strains studied, the OSU strain
was found to be most virulent and UKtc strain the least virulent. The CD-
1 strain of mouse was found to be the most susceptible to virus infection
and C57/BL the least susceptible.
A very simple and rapid nucleic acid extraction method has been
developed that requires only one centrifugation step and circumvents the
use of any hazardous organic chemicals, which can be applied to very
large numbers of samples saving time and labour.
Rotavirus reassortants were constructed in a variety of ways and
their genotype determined from relative mobility of their gene segments
on polyacrylamide gels and restriction enzyme digestion of PCR
amplified products. Twenty two reassortants (2%) were identified out of
more than 1100 progeny clones examined and these reassortants belonged
to 15 different genotypes. Possible reasons for obtaining this low number
of reassortants are discussed. No reassortant could be identified between
a murine rotavirus and other heterologous rotavirus strains. Preliminary
sequence of VP7 gene of murine rotavirus strains, EDIM and EBR, was
found to be different to the published rotavirus sequences including the
recently published five murine rotavirus strains.
The virulence mapping studies conducted in mice with some of the
22 reassortants obtained in the present study showed that gene 4 of the
OSU and UKtc strains was involved in virulence. Segment 5 of OSU
strain and segments 5, and 8 of UKtc strain may also be involved in
virulence.

Item Type:	Thesis (PhD)
Subjects:	Q Science > QR Microbiology > QR355 Virology
Library of Congress Subject Headings (LCSH):	Rotaviruses -- Genetics, Rotavirus infections -- Vaccination, Virulence (Microbiology)
Official Date:	February 1995
Dates:	Date Event February 1995 Submitted
Institution:	University of Warwick
Theses Department:	Department of Biological Sciences
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	McCrae, M.
Sponsors:	Commonwealth Scholarship Commission in the United Kingdom ; University of Warwick
Extent:	xxii, 255 leaves
Language:	eng

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