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Reovirus research
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We use a variety of cell biological, biochemical and virological tools to investigate the following questions about reovirus factories:
How are viral factories assembled? - We know that the matrix of the viral factory is formed by the viral nonstructural protein mNS and that the factories are linked to cellular microtubules via the viral structural protein m2. We are now investigating the kinetics of factory formation and their effect on microtubule dynamics and transport.
  
What are the factory's functions and how do they promote viral replication? - The viral core particles appear to assemble within the factories. One function of the factory therefore might be to recruit the viral structural proteins needed for core assembly. We are investigating which viral proteins are recruited to the factories.
  

What viral and cellular proteins are recruited to the factories? - The viral proteins m2 and sNS are recruited to the factories. Cellular proteins are also likely found within the factories. We are investigating the protein composition of factories and relating this functionally to viral replication.

  

What cytopathologic effect do the factories have on the infected cell? - The viral factories are similar in many respects to cellular aggresomes. Aggresomes are collections of aggregated protein that form inclusions within cells. The aggresome adversely affects proteasome function. We are investigating the effect of viral factories on proteasome and other cellular functions.

  

Schematic of the reovirus replication cycle
         
   

Reoviruses replicate in the cytosol of infected cells. Following penetration of the cellular membrane, viral cores begin transcribing the 10 viral genome segments. The 10 viral genome segments encode 12 viral proteins (8 structural and 4 nonstructural). The nonstructural protein mNS forms the matrix of viral factories where new cores assemble and begin secondary rounds of transcription. The viral cores are coated with the outer capsid proteins m1, s3, and s1 to form intact virions that are released following cell lysis.