Retroviral infection and expression of cationic amino acid transporters in rodent hepatocytes.
The susceptibility of rodent hepatocytes to infection by mouse type C retroviruses was examined in vivo and in vitro and compared with the expression of two membrane proteins that function as transporters for the cationic amino acids CAT-1 and CAT-2. CAT-1 expression in rodents determines susceptibility to ecotropic retrovirus infection by serving as the virus receptor. Recently, it has been suggested that CAT-2 may be a receptor for amphotropic murine leukemia virus. In the present study, CAT-1 expression was observed in Hepa1, a cell line derived from a murine hepatoma, and in rat hepatocytes propagated on collagen monolayers in vitro but not in intact or regenerating rat liver in vivo. The expression of CAT-1 correlated with susceptibility to infection by an ecotropic retrovirus encoding beta-galactosidase. CAT-2 expression was observed in hepatocytes in vitro and in vivo, consistent with reports of infection of regenerating and cultured hepatocytes by amphotropic retroviruses. However, introduction of murine CAT-2 into nonpermissive Chinese hamster cells was not sufficient to confer susceptibility to amphotropic retrovirus infection, using a protocol that could easily demonstrate CAT-1-dependent infection by an ecotropic virus. Our data establish CAT-1 as a major determinant of ecotropic retrovirus infection in rodent hepatocytes and suggest that CAT-2 is not a receptor for viruses in the amphotropic subgroup.
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
E I
EI
Closs
I H
IH
Borel Rinkes
A
A
Bader
M L
ML
Yarmush
J M
JM
Cunningham
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D015686:Gene Products, env / Q000378:metabolism; D066298:In Vitro Techniques; D009052:Leukemia Virus, Murine / Q000254:growth & development*; D007942:Leukemia, Experimental / Q000382:microbiology*; D008099:Liver / Q000382:microbiology; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D011991:Receptors, Virus; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014779:Virus Replication
D002352:Carrier Proteins; D015686:Gene Products, env; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D011991:Receptors, Virus; D011994:Recombinant Proteins; C070506:ecotropic murine leukemia virus receptor