Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the contribution of the myxoma virus M-T4 gene to viral virulence, both copies of the M-T4 gene were inactivated by disruption and insertion of the Escherichia coli guanosine phosphoribosyltransferase gene. Infection of European rabbits with the recombinant M-T4-deleted virus, vMyxlacT4, resulted in disease attenuation. In contrast, infection of rabbits with vMyxlac elicited the classical features of lethal myxomatosis. A notable decrease in the number of secondary lesions in animals infected with vMyxlacT4 suggested an inability of the virus to disseminate in vivo. Infection of either a rabbit CD4+ T cell line, RL-5, or primary rabbit peripheral blood lymphocytes with vMyxlacT4- resulted in the rapid induction of apoptosis. Sequence analysis of M-T4 revealed both an N-terminal signal sequence and a C-terminal -RDEL sequence, suggesting that M-T4 resides in the endoplasmic reticulum. The M-T4 protein was found to be sensitive to endo H digestion and confocal fluorescence microscopy demonstrated that M-T4 colocalized with calreticulin, indicating that M-T4 is retained within the endoplasmic reticulum. Our results indicate that M-T4 is the first example of an intracellular virulence factor in myxoma virus that functions from within the endoplasmic reticulum and is necessary for the productive infection of lymphocytes.
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PMID:The myxoma virus M-T4 gene encodes a novel RDEL-containing protein that is retained within the endoplasmic reticulum and is important for the productive infection of lymphocytes. 943 27