The Kunkel legacy and hepatitis C virus infection

Abstract

In commemoration of Henry Kunkel's 100th birthday, the effect of his legacy on the investigation of hepatitis C virus is recounted. The delineation of a major cross-idiotype (WA) among patients with essential mixed cryoglobulinemia led to the discovery that HCV was the etiologic agent for this disease. Studies of the cryoglobulins led to the discovery that WA RF reacted specifically with HCV-VLDL like particles that on electronmicroscopy and binding studies appeared to be the virion within a lipid shell. This particle mediates cell entry via LDLr and may serve to avoid the immune response by masking the virion. In addition, the WA B cell may be a prognostic marker for cutaneous vasculitis and B cell malignancy in HCV-infected patients. In commemoration of Henry Kunkel's 100th birthday, this is an account of how his legacy had a role in the investigation of hepatitis C virus (HCV) infection. There is a bit of a historical basis for the legacy of this great immunologist having a role in virology. He began his research career studying hepatitis. Later he worked with HCV in his studies of mixed cryoglobulins although he didn't know it at the time. There may also have been a Kunkel historical basis for why he accepted me as fellow in his laboratory considering that my credentials paled in comparison with those of the fellows and PhD students in his laboratory. Like Henry I was drafted into the Navy following my internship, I had had minimal research experience in medical school and only one minor publication, and I had a passion for clinical investigation. It may have been fortuitous that while on active duty at the Bayonne NJ Naval Base I visited Henry Kunkel in my Navy uniform and told him I was interested in studying SLE. I did not know at the time the dramatic role the Navy had played in his career or that one of his major training goals was to teach MDs to use clinical observation as a focus for delineating disease mechanisms in the laboratory. When I started work in the laboratory on discharge from the Navy, the first thing he told me was that it took five years to make a clinical investigator so I might as well get a Rockefeller University PhD while working in his laboratory. I was sure I would leave the laboratory after two years so I declined his offer. I did not leave until six years later!

Keywords: B-cell malignancy; Cryoglobulinemia; Cryoglobulinemic vasculitis; Hepatitis C virus; Immunoglobulin idiotypes; Monoclonal rheumatoid factors.