UDP-galactose transporter is required for Theiler's virus entry into mammalian cells.
Theiler's murine encephalomyelitis viruses (TMEV) are divided into two groups: high-neurovirulence strains, such as GDVII, cause fatal encephalitis, while low-neurovirulence strains, such as BeAn and DA, cause persistent infection and demyelination in mice. Cell surface sialic acid is bound by the low-neurovirulence DA and BeAn viruses, but not by the high-neurovirulence GDVII virus. We have identified a clone from a BHK-21 cell cDNA library that mediates TMEV entry and infection by viruses of both TMEV groups in a receptor-negative BHK-21 cell variant (R26). The sequence of this clone is 96.4% identical to the human UDP-galactose transporter (UGT), which belongs to a family of nucleotide-sugar transporter proteins involved in the biosynthesis of complex carbohydrate structures in the trans-Golgi network. UGT mRNA from R26 cells was found to have a 490-nucleotide deletion involving the C-terminal amino acids 255 to 392 and 81 nucleotides of the 3' noncoding region. These results suggest two possibilities by which UGT may mediate TMEV entry and infection. The most likely one relates to the transporter function of adding galactose to another receptor protein. This possibility suggests the requirement for a specific glycoprotein interaction for GDVII virus cell binding and entry, e.g., galactose for GDVII and sialic acid for BeAn. Alternatively, UGT might be a TMEV receptor itself, acting via UGT cycling to the cell surface.
Hertzler
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S
Integrated Graduate Program, Northwestern University Medical School, Chicago, Illinois, USA.
Kallio
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P
Lipton
H L
HL
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018188:Cardiovirus Infections / Q000821:virology*; D002460:Cell Line; D006224:Cricetinae; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017945:Theilovirus / Q000472:pathogenicity* / Q000502:physiology; D014162:Transfection; D014774:Virulence; D000099237:UDP-Galactose Translocators
D009004:Monosaccharide Transport Proteins; D011991:Receptors, Virus; D000099237:UDP-Galactose Translocators