Cell Biology, Genetics and Biochemistry of RNA Viral Propagation
For many subcellular viruses and parasites, RNA, not DNA,
is the carrier of genetic information. This has several interesting
consequences for the genetics and biology of these genomes.
For poliovirus for example, the mechanism of genetic recombination
is vastly different from the breaking-and-rejoining found in DNA
genomes, occuring instead by template switching by the viral
RNA-dependent RNA polymerase, 3D. For RNA genomes like that
of poliovirus that propagate in the cytoplasm of infected eukaryotic
host cells, the colocalization of genome replication and translation
of proteins makes possible direct coupling of this process so
that it is likely that several encoded proteins act predominately
in cis. To make infected cells more habitable environments,
many RNA viruses engineer drastic reorganizations of both
nuclear and cytoplasmic compartments.
Our laboratory is taking the following approaches to investigate
the cell biology, genetics and biochemistry of RNA viral propagation,
using poliovirus as a model system: (i) Based on the three-dimensional structure of the poliovirus
polymerase determined in the laboratory of Steve Schultz
(U. Colorado, Boulder), we are identifying amino acid residues
and protein surfaces involved in binding RNA, other viral proteins
and host cell proteins during RNA synthesis within infected cells.
(ii) Using both in vitro assays for viral growth and infections of
tissue-culture cells with genetically engineered viruses, we are
investigating the genetics of each of the viral coding regions and
the mechanism of RNA recombination.
(iii) We are employing both in vitro assays for protein secretion
and ultrastructural and biochemical analysis of cells that express
individual poliovirus proteins to understand the mechanisms of
cytoplasmic reorganization during viral infection. It is likely that
viruses such as poliovirus exploit existing cellular mechanisms
to construct structures useful to the virus during infection.
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