Viruses and Autoimmunity
Ian A. York
york at mbcrr.dfci.harvard.edu
Sat Feb 4 20:15:33 EST 1995
In article <3gtms2$rs2 at mserv1.dl.ac.uk> <n.panjwani at ic.ac.uk> writes:
>Are there mechanisms, other than molecular mimicry of host proteins, by
>which viruses can induce autoimmunity, ie. by direct interaction of viral
>products (cytokine homologues, receptor homologues, etc.) with the host
Well, as I recall, the lpr mouse develops its hyperactive immune
responses because it has a retrovirus insertion disrupting its fas gene.
I'm far from an expert on the subject, but here are a few thoughts:
I have a vague memory of autoimmunity being induced by viral destruction
of host cells; in this case, although the virus doesn't mimic host
proteins directly, it allows the immune system to sample proteins it
otherwise might never be exposed to. One possible situation here might be
in HCV infection, in which autoantibodies to liver microsomal and
cytoplasmic proteins have been found (e.g. Autoimmunity. 17(2):89-97,
There are also links between viral infection and subsequent autoimmune
respopnses to myelin basic protein (e.g. Mokhtarian F. Shi Y. Zhu PF.
Grob D. Immune responses, and autoimmune outcome, during virus infection
of the central nervous system. Cell Immunol. 157(1):195-210, 1994). It
is far from clear to me whether this is directly caused by the virus or
whether it's a side-effect of an overexcited immune system; I don't know
if you would draw a distinction between those in your definition.
Other candidates for your pet would be those viruses which infect
lymphocytes, presumably, and which alter the activation state, or prevent
apoptosis, of the infected lymphocytes. So candidates for this activity
would include EBV (I note that apparently levels of autoantibodies
increase in immunosuppressed patients with EBV-associated
lymphoproliferative diseases) and HTLV and other retroviruses (see: (1)
Wilder RL. Hypothesis for retroviral causation of rheumatoid arthritis.
Curr Opin Rheumatol. 6(3):295-9, 1994.; (2) Fukui T. Sugita K.
Ichikawa H. Negishi A. Kasai H. Tsukagoshi H. Human T lymphotropic
virus type I associated myelopathy and myasthenia gravis: a possible
association?. Eur Neurol. 34(3):158-61, 1994.)
HIV is also associated with autoantibodies; I don't know if outright
autoimmunity is seen, perhaps because there isn't enough of an immune
reponse left by the time they show up. Pathogenesis in HIV is so poorly
understood that I wouldn't spend a lot of time on this as an example.
Measles virus also is lymphotrophic, and postmeasles encephalitis is (I
think) believed to be a result of immune dysregulation (Johnson RT. The
virology of demyelinating diseases. Ann Neurol. 36 Suppl:S54-60,
Another category that might fit your definition is the superantigen
effect. Again there doesn't seem to be any black-and-white answer, but
there are certainly people considering this. (Yoshimoto T. Nagase H.
Nakano H. Matsuzawa A. Nariuchi H. A V beta 8.2-specific superantigen
from exogenous mouse mammary tumor virus carried by FM mice. Eur J
Immunol. 24(7):1612-9, 1994).
Hope this at least provides some ideas.
Ian York (york at mbcrr.harvard.edu)
Dana-Farber Cancer Institute, 44 Binney St., Boston MA 02115
Phone (617)-632-4328 Fax (617)-632-2627
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