R. Frank Ramig, Ph.D.
Department of Molecular Virology & Microbiology
Genetics of Viral Replication and Pathogenesis
Dr. Ramig's research interests focus on the genetics, replication and pathogenesis of the Reoviridae; a large family of viruses whose unique feature is a genome consisting of discrete segments of double-stranded RNA. His laboratory uses a genetic approach to understand in molecular detail the function of the individual genes in viral replication at the level of the infected cell. We also examine the functions of those genes during infection of the multicellular host, where tissue tropisms and other pathogenic mechanisms come into play. We also use a cell-free system to examine the mechanisms of viral RNA synthesis, particularly synthesis of the negative strand of the double-stranded genome RNA. Our current model system is the rotaviruses; investigations fall into three areas.
Rotavirus temperature-sensitive mutants were isolated and characterized. These mutants continue to be exploited in studies of specific aspects of viral replication and assembly. We are interested in trans-complementation of mutant proteins by host cells expressing wild-type forms of the viral proteins. We are also interested in identifying signals on the RNAs that allow rotaviruses to form reassortants by reassortment.
Rotavirus strains with different pathogenic phenotypes in a mouse model system have been identified and are being exploited to identify viral genes responsible for a variety of the pathogenic phenotypes. We are currently focusing on issues of extra-intestinal spread of rotaviruses, with emphasis on spread to the liver. We recently showed that a viral nonstructural protein plays a critical role in liver infection by strains able to escape the gut and infect the liver.
We developed an in vitro system capable of replicating rotavirus genome RNA. We applied this system, together with deletion, mutant and chimeric template RNAs, to identify cis-acting replication signals on pre-genomic mRNA that regulate its replication. We are currently examining the potential roles of RNA structure, viral nonstructural proteins and host cell factors in viral RNA replication. We are also exploring the use of the replication system in development of a “reverse genetic” system for the rotaviruses. Development of reverse genetics would allow us to examine the effects of site-directed engineered mutations during virus infection of cultured cells or animals, an approach that is not currently possible for any member of the Reoviridae..
Department of Molecular Virology & Microbiology
Baylor College of Medicine
One Baylor Plaza, MS BCM385
Houston, TX, 77030, U.S.A.
Ph.D. - University of Colorado, Boulder
Postdoctoral - Albert Einstein College of Medicine, NY and Harvard Medical School, Boston
Awards, Appointments and Honors
1991 Division T (RNA viruses) Lecturer, Annual Meeting of the American Society for Microbiology
1993 The Chancellor’s Visiting Professorship in Biology, University of Maryland
1997 US Patent, “An in vitro replication system capable of rescuing cloned and manipulated rotavirus genes”
Ramig, R.F. (2004) Pathogenesis of intestinal and systemic rotavirus infection. Journal of Virology 78: 10213-10220.
Mossel EC, Ramig RF (2003) A lymphatic mechanism of rotavirus extraintestinal spread in the neonatal mouse. Journal of Virology 77: 12352-12356.
Pesavento JB, Billingsley A, Roberts E, Ramig RF and Prasad BVV. (2003) Reassortant rotavirus structures illustrate the relationship between VP4 origin and the recovery of viral infectivity. Journal of Virology 77: 3291-3296.
Mossel EC, Ramig RF (2002) Rotavirus genome segment 7 (NSP3) is the determinant of extraintestinal spread in the neonatal mouse. Journal of Virology 76: 6502-6509.
Taraporewala AF, Schuck P, Ramig RF, Patton JT (2002) Analysis of a rotavirus temperature-sensitive mutant indicates that NSP2 octamers are the functional form of the protein. Journal of Virology 76: 7082-7093.
Crawford SE, Mukherjee SK, Estes MK, Lawton JA, Shaw AL, Ramig RF, and Prasad BVV. 2000. Trypsin cleavage stabilizes the rotavirus VP4 spike. Journal of Virology 75: 6052-6061
Ramig RF. 1997. Genetics of the rotaviruses. Annual Review of Microbiology 51:225-255.
Ramig RF 1997. Suppression and reversion of mutant phenotype in reovirus. Current Topics in Microbiology and Immunology, Vol 233/1, KL Tyler and MBA Oldstone, Eds., Springer-Verlag, Berlin, pp 110-135.
Wentz M, Patton JT and Ramig RF. 1996. The 3´-terminal consensus sequence of rotavirus mRNA is the minimal promoter of negative-strand synthesis. Journal of Virology 70:7833-7841.
Chen D, Zeng CQ-Y, Wentz M, Gorziglia M, Estes M and Ramig RF. 1994. Template-dependent, in vitro replication of rotavirus RNA. Journal of Virology 68:7030-7039.
Model for Regulation of RNA Replication by Localization of NSP3 and VP1