Re: Deaths From WNV May Be Tied to a Gene Variation

<x-flowed>.... and this one says it's in the virus:

Virology 2002 Apr 25;296(1):17-23

Mouse neuroinvasive phenotype of West Nile virus strains varies depending
upon virus genotype.

Beasley DW, Li L, Suderman MT, Barrett AD.

Department of Pathology, The University of Texas Medical Branch, Galveston,
Texas 77555-0609, USA.

Despite recent advances in the genetics of West Nile (WN) virus, relatively
little is known about the molecular basis of virulence of this virus. In
particular, although the genotype of the WN virus strain that was recently
introduced into North America has been determined, there have been few
experimental studies on the virulence phenotype of the virus. We compared
genetic and neurovirulence properties of 19 strains of WN virus, including 2
from North America, and observed significant differences in their
neuroinvasive phenotype in mice and hamsters that correlated with virus
genotype. Virus isolated in North America was found to be highly
neuroinvasive with a lack of age-related resistance to infection in mice
normally associated with mosquito-borne flaviviruses.
==============

Then again, there is the wide variety of external factors which may impair
immunocompetence, such as:

J Med Virol 2002 Apr;66(4):576-80
Inhalation anesthetic-induced neuroinvasion by an attenuated strain of West
Nile virus in mice.

Katz Y, Lustig S, Ben-Shlomo I, Kobiler D, Ben-Nathan D.

Laboratory for Research in Anesthesia, Pain and Neuroscience, Bruce
Rappaport Faculty of Medicine, Technion-Israel Institute of Technology,
Haifa, Israel. ykatz18@hotmail.com

There are contradictory reports regarding the effects of inhalation
anesthetics on the immune system. Measurable immune responses have been
studied in vitro, but little is known about the in vivo effects in the
intact organism. We used an attenuated, non-neuroinvasive, nonlethal strain
of the encephalitic West Nile virus, termed WN-25, which can become lethal
in combination with environmental stressors, to study possible modulatory
immune effects of inhalation anesthetics in mice. Both single short-term
exposure and repeated exposure to halothane and nitrous oxide were studied.
Exposure to 30% CO2 served as a positive control. Mortality, brain invasion,
spleen weight, and antiviral antibodies served as the experimental
endpoints. Halothane and nitrous oxide led to viral brain invasion,
increased mortality, and suppressed immune response in a concentration- and
time-dependent manner. Repeated exposures had a cumulative effect.
Assessment of the stability of the viral attenuation did not demonstrate any
alteration in the character of the virus, suggesting an increased access to
the brain by inhalation anesthetics that led to the fatal encephalitis.
These findings may be of special concern to populations at risk, such as
operating room staff and patients undergoing general anesthesia in endemic
areas of encephalitic virus species, in which subclinical infection may
develop into an overt disease. Copyright 2002 Wiley-Liss, Inc.
==============

and worst of all, resistance to neuroinvasion may come with a price tag!:

Mol Psychiatry 2001 Nov;6(6):701-11

A novel mechanism to explain protein abnormalities in schizophrenia based on
the flavivirus resistance gene.

Brown JS Jr.

Mental Health Service Line, McGuire Veterans Administration Medical Center,
1201 Broad Rock Blvd, Richmond, VA 23249, USA. jbrown2185@aol.com

The geographical distribution of schizophrenia was previously shown to
correlate with the global distribution of tick-borne flaviviruses. The
correlation suggests a natural resistance gene to flaviviruses could be
involved in schizophrenia. The flavivirus resistance gene, Flv, a gene found
in wild mice and certain in-bred strains, confers resistance to flaviviruses
through the interaction of cellular proteins with the flaviviral 3'
untranslated regions (UTRs). Although the sequence and product of Flv are
unknown, translation elongation factor alpha-1 (EF-1) is a protein known to
interact with the 3' UTR flavivirus RNA, forming some complexes with long
half-lives that inhibit RNA growth. A study was performed to assess the
homology between flaviviral UTRs, subunits of EF-1, and selected proteins
reported as abnormal in schizophrenia. The UTRs of four flaviviruses with
wide geographical and phylogenic distribution were manually translated.
Using the National Biomedical Research Foundation protein databank, the
amino acid sequences were correlated with the amino acid sequences of
selected proteins. The amino acid sequences of the EF-1 subunits were then
correlated with the same proteins. Similar amino acid correlations between
the proteins, EF-1 subunits and viral UTRs suggest that translational
pathophysiology resulting from the product of Flv can be postulated as the
cause of protein abnormalities observed in schizophrenia.

Eleanor Kellon, V.M.D.

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