IS HEPATITIS C VIRUS A SIALODACRYOADENITIS
essential mixed cryoglobulinemia, which itself is a major extrahepatic manifestation of HCV infection.
VIRUS?
Genetic factors have been implicated in both Sjo Β¨gren's syn-Koike K, Moriya K, Ishibashi K, Yotusyangi H, Shintani Y, drome and essential mixed cryoglobulinemia. Considering Fujie H, Kurokawa K, et al. Sialadenitis Histologically Resemthe uncommon occurrence of both manifestations in the bling Sjo Β¨gren Syndrome in Mice Transgenic for Hepatitis C same HCV-infected patient, one possible explanation for the Virus Envelope Genes. Proc Natl Acad Sci U S A association is the coincidental occurrence in HCV-infected 1997;94:233-236. (Reprinted with permission.) patients of the independent genetic factors that may predispose to mixed cryoglobulinemia and Sjo Β¨gren's syndrome. The animal model may be instructive in this regard, in that it
Abstract
suggests a viral rather than an autoimmune process in the Hepatitis C virus (HCV), a major causative agent of nonsialodacryoadenitis and provides additional evidence against A, non-B chronic hepatitis, has also been suggested to be a direct role of HCV in Sjo Β¨gren's syndrome.
associated with extrahepatic manifestations such as mixed
Overall, the observations of Koike et al. suggest that HCV cryoglobulinemia and glomerulonephritis. Two independent envelope proteins evoke inflammation in salivary and lacrilines of transgenic mice carrying the HCV envelope genes mal glands and that sialodacryoadenitis in HCV transgenic have been shown previously to express the HCV envelope mice is similar to that in HCV-infected human beings. The proteins in organs, including the liver and salivary glands, lesions, although much less severe, resemble those produced which results in no pathological changes in the liver. Further by the mumps virus in human beings and the sialodacryoadeanalysis of these animals now has revealed that they develop nitis virus in rats 3 in that the ductal epithelium is primarily an exocrinopathy involving the salivary and lachrymal glands. involved. There are, however, some general and specific res-This pathology resembles Sjo Β¨gren syndrome, which also is ervations regarding this model.
suggested to have a possible association with chronic hepatitis
In the past few years, transgenic mouse models have been C. These observations suggest that HCV might be involved applied to the study of HCV infection. In general, there have in the pathogenesis of sialadenitis in humans and that this been concerns regarding the physiologic significance of these transgenic mouse system would be a good animal model for models, either because the replication of HCV was not acthe study of HCV infection.
complished or because the complete HCV genome was not expressed. In the model developed by Koike et al., HCV envelope proteins were expressed at a much higher level COMMENTS