Effects of transforming growth factor-alpha (TGF-alpha) in vitro and in vivo on reovirus replication.

Organ EL, Nalbantyan CD, Nanney LB, Woodward SC, Sheng J, Dubois RN, Price J, Sutcliffe M, Coffey RJ, Rubin DH
DNA Cell Biol. 2004 23 (7): 430-41

PMID: 15294092 · DOI:10.1089/1044549041474751

We have utilized growth factors in in vitro and in vivo systems to examine the role of cellular proliferation in reovirus replication. In vitro, proliferating RIE-1 cells can be infected with whole reovirus virions, but are relatively resistant to infection once confluent (Go arrest). It has been shown that TGF-alpha, which signals through the EGF-receptor (EGF-R), is capable of dramatically increasing the number of RIE-1 cells entering the S-phase in the presence of additional serum factors. Stimulation of the EGF-R without serum results in minimal increases in cells entering the S-phase with a restriction in reovirus replication. Therefore, other factors in serum are essential for fully permissive infection. In vivo, we used metallothionein (MT) promoter/enhancer-TGF-alpha transgenic mice to study the effect of cytokine activation on reovirus type 1 infection. Virus replication decreased following oral infection in these transgenic mice at 1 month of age, concordant with increased mucin production. Titers of reovirus obtained from the livers of 1 year old transgenic mice were approximately 10-fold higher than titers obtained in control mice. Taken together, these data indicate that while growth factor activation ultimately leads to an increase in virus infectivity, other factors may be necessary for reovirus replication.

MeSH Terms (20)

Animals Cell Membrane Cells, Cultured Culture Media ErbB Receptors Gene Expression Regulation Insulin Intestines Liver Metallothionein Mice Mice, Transgenic Promoter Regions, Genetic Rats Reoviridae Reoviridae Infections Signal Transduction S Phase Transforming Growth Factor alpha Virus Replication

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