We plan to continue our investigations into the genetics and pathogenesis of the rotaviruses, with the long-term goal of defining, at a molecular level, the roles of the viral genes that control various aspects of pathogenesis. This information will be useful in formulation of strategies for the control of rotavirus-induced disease. In addition, these studies will provide basic information on the interaction of enteric viruses with the host, and may reveal unique pathogenic pathways characteristic of rotavirus infection. Research on the """"""""genetics of the rotaviruses"""""""" will focus on four main areas. (1) Studies of basic rotavirus genetics will include the following: We will complete our phenotypic analysis of temperature-- sensitive (ts) mutants by characterizing the viral transcriptase and guanlyltransferase. We will determine the sequence of genome segment 4 from the tsA mutants (map to segment 4) to determine the basis of the protease-concentration-dependent expression of ts phenotype by some group A mutants. We will initiate studies of genetic isolation mechanisms within the group A rotaviruses, concentrating on the apparent isolation of the avian viruses in serotype 7 from the other group A viruses. (2) We will continue our studies of rotavirus variability, concentrating on the genome segment rearrangements identified in persistent infections of permissive cells with the tsB mutant, but not in persistent infections with other mutants. (3) We will continue our recently-initiated studies of the morphology and assembly of rotavirus particles. These studies will investigate the nature of the interactions between reassortant proteins of heterologous origin that modulate the expression of viral phenotypes such as protease-sensitivity and neutralization. We will also continue our studies of virus assembly with the goal of reconstituting virus from virion-derived subunits as a means of effecting rescue of exogenous genes. Finally, (4) we will continue our studies of rotavirus pathogeneis and virulence. These studies will use the suckling mouse model to identify viral genes controlling (a) disease production as measured by DD50, (b) virus replication in the intestine, and (c) gene products eliciting neutralizing responses in primary and secondary infections. We will also continue our studies of the determinants of active and passive protection in the mouse model. We will also pursue our ongoing work to identify viral genes responsible for the extra-intestinal spread of some rotaviruse strains in vivo, and for ability of some strains to infect hepatic cells (HepG2) in vitro.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI016687-15
Application #
2060388
Study Section
Experimental Virology Study Section (EVR)
Project Start
1984-07-01
Project End
1998-02-28
Budget Start
1994-03-01
Budget End
1995-02-28
Support Year
15
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Biochemistry
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030