Effects of transforming growth factor-alpha (TGF-alpha) in vitro and in vivo on reovirus replication.
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.
Organ
Edward L
EL
Department of Research Medicine, VA Tennessee Valley Healthcare System, Nashville, USA.
Nalbantyan
Christopher D
CD
Nanney
Lillian B
LB
Woodward
Stephen C
SC
Sheng
Jinsong
J
Dubois
Raymond N
RN
Price
James
J
Sutcliffe
Marilyn
M
Coffey
Robert J
RJ
Rubin
Donald H
DH
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003470:Culture Media; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D007328:Insulin / Q000494:pharmacology; D007422:Intestines / Q000166:cytology / Q000821:virology; D008099:Liver / Q000821:virology; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D051381:Rats; D012087:Reoviridae / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D012088:Reoviridae Infections / Q000235:genetics; D016196:S Phase / Q000187:drug effects; D015398:Signal Transduction; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
D003470:Culture Media; D007328:Insulin; D016211:Transforming Growth Factor alpha; D008668:Metallothionein; D066246:ErbB Receptors