Research Program - Sin Nombre virus (a hantavirus)

Transmission of Sin Nombre virus

Sin Nombre virus (SNV) is an etiologic agent of a human disease called hantavirus pulmonary syndrome (HPS) or hantavirus cardiopulmonary syndrome. The disease was recognized in spring 1993 when dozens of people in the Four Corners area were affected and nearly 60% of them died. The case-fatality rate of HPS is now about 37% because of more rapid recognition and diagnosis of less severe cases. Hantaviruses (family Bunyaviridae, genus Hantavirus) other than SNV have been shown to cause this disease not only throughout North America but in Central and South America as well. Nearly 40 hantaviruses are now recognized throughout the world; some cause HPS, some cause the long-recognized hemorrhagic fever with renal syndrome, and the rest are not (yet?) known to cause disease. Each of these viruses is associated with a specific primary rodent host, suggesting a coevolutionary phenomenon. The rodent host is minimally or not at all infected by the virus it carries. Indeed, while the rodent host produces antibody to the virus, it maintains a persistent infection, with some of these rodents shedding virus persistently and others, most, not shedding virus but harboring it in their tissues.

For the past 13 years studies of SNV have been conducted by Dr. Charles Calisher, CSU's Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, in cooperation with the U.S. Centers for Disease Control and Prevention and the National Institutes of Health.

In an effort to elucidate the mode and characteristics of transmission of SNV, from 1994 to 1996, Dr. Charles Calisher and associates trapped rodents at the SJBRC each 6 weeks from late spring to early fall.  Much of the data resulting from these and associated studies, regarding not only SNV but deer mouse biology and other aspects of field studies as well, have been published in the scientific literature and more will appear as the massive data base is evaluated.

These and other studies have resulted in a cascade model of SNV amplification and transmission. That model emphasizes the importance of the effects of meteorological factors on food products. We recently demonstrated that diet can dramatically affect urinary pH of deer mice, a hitherto overlooked factor that could condition SNV viability, excretion, and shedding (transmission potential). In brief sum,

1. environmental factors likely influence maintenance and transmission of SNV,
2. meteorological factors influence rodent food quantity and quality,
3. diet effects host physiology, including urinary pH,
4. urinary pH may affect virus stability and transmission, and
5. these factors may converge to impact transmission of SNV among deer mice.

Currently, we are testing the fundamental hypothesis that seasonal dietary intake indirectly affects the stability and shedding of SNV and thereby influences SNV transmission between deer mice. If this is shown to be correct, we will be better able to understand virus-rodent-host interaction dynamics and to provide better warning systems to prevent human disease.

Publications (names in bold are CSU personnel/investigators)

Root, J.J., C.H. Calisher, and B.J. Beaty. Relationships of deer mouse movement, vegetative structure, and prevalence of infection with Sin Nombre virus. J. Wildl. Dis., 35: 311-318, 1999.

Calisher, C.H., W.P. Sweeney, J.J. Root, and B.J. Beaty. Navigational instinct: A reason not to live-trap deer mice in residences. Emerg. Inf. Dis., 5:175-176, 1999.

Calisher, C.H., W. Sweeney, J.N. Mills, and B.J. Beaty. Natural history of Sin Nombre virus in western Colorado. Emerg. Inf. Dis., 5: 126-134, 1999. http://www.cdc.gov/ncidod/eid/vol5no1/calisher.htm

Calisher, C.H., Childs, J.E., Sweeney, W.P., Canestorp, K.M., and Beaty, B.J., Dual captures of Colorado rodents: implications for transmission of hantaviruses. Emerg. Infect. Dis., 6: 363-369, 2000. http://www.cdc.gov/ncidod/eid/vol6no4/calisher.htm

Root, J.J., Calisher, C.H., and Beaty, B.J. Microhabitat partitioning by two chipmunk species (Tamias) in western Colorado. Western North American Naturalist 61:114-118, 2001.

Calisher, C.H., Mills, J.N., Sweeney, W., Choate, J.R., Sharp, D.E., Canestorp, K.M., and Beaty, B.J. Do unusual site-specific population dynamics of rodent reservoirs provide clues to the natural history of hantaviruses? J. Wildl. Dis. 37:280-288, 2001.

Calisher, C.H., Nabity, S., Root, J.J., Fulhorst, C., and Beaty, B.J. Transmission of an arenavirus in white-throated woodrats (Neotoma albigula), southeastern Colorado. Emerg. Inf. Dis. 7:397-402, 2001.

Nisbett, R.A, Caire, W., Stuart M.D., Caddell, G.M., Crutcher, J.M., and Calisher, C.H. Serologic survey of Oklahoma rodents: evidence for the presence of a hantavirus and an arenavirus. Proc. Okla. Acad. Sci. 81:53-66, 2001.

Frey, J.K., Root, J.J., Jones, C.A., Calisher, C.H., and Beaty, B.J. New records of the Mogollon vole, Microtus mogollonensis (Mearns 1890), in southwestern Colorado. Western N. Amer. Naturalist. 62:120-123, 2002.

Calisher, C.H., Root, J.J., Mills, J.N., and Beaty, B.J. Assessment of ecologic and biologic factors leading to hantavirus pulmonary syndrome, Colorado, U.S.A., Croatian Med. J. 43:330-337, 2002. http://www.cmj.hr/2002/43/3/12035141.pdf

Yates, T.L., Mills, J.N., Parmenter, C.A., Ksiazek, T.G., Parmenter, R.R., Vande Castle, J.R., Calisher, C.H., Nichol, S.T., Abbott, K.D., Young, J.C., Morrison, M.L., Beaty, B.J., Dunnum, J.L., Baker, R.J., Salazar-Bravo, J., and Peters, C.J. The ecology and evolutionary history of an emergent disease: hantavirus pulmonary syndrome. BioScience, 52:989-998, 2002.

Calisher, C.H., Mills, J.N., Root, J.J., and Beaty, B.J. Hantaviruses: etiologic agents of rare, but potentially life-threatening, zoonotic diseases. J. Am. Vet. Med. Assoc. 222:163-166, 2003.

Root, J.J., Black, W.C., Calisher, C.H., Wilson, K.R., Mackie, R.S., Schountz, T., Mills, J.N., and Beaty, B.J. Analyses of gene flow among populations of deer mice (Peromyscus maniculatus) at sites near hantavirus pulmonary syndrome case-patient residences. J. Wildl. Dis. 39:287-298, 2003.

Schountz, T., Green, R., Davenport, B., Buniger, A., Richens, T., Root, J.J., Davidson, F., Calisher, C.H., and Beaty, B.J. Cloning of multiple deer mouse (Peromyscus maniculatus) cytokine and chemokine cDNAs. BMC Immunology 5:1, 2004. http://www.biomedcentral.com/1471-2172/5/1

Root, J. J., Black IV, W.C., Calisher, C.H., Wilson, K.R. and B. J. Beaty. Genetic relatedness of deer mice (Peromyscus maniculatus) infected with Sin Nombre virus. Vector-Borne Zoon. Dis. 4:149-157, 2004.

Root, J.J., Wilson, K.R., Calisher, C.H., Wagoner, K., Abbott, K.D., Yates, T.L., Kuenzi, A.J., Morrison, M.L., Mills, J.N., and Beaty, B.J.. Spatial clustering of murid rodents infected with hantaviruses: implications from meta-analyses. Ecological Applications 15:565-574, 2005.

Calisher, C.H., Mills, J.N., Sweeney, W., Root, J.J., Reeder, S.A., Jentes, E.S., and Beaty, B.J. Population dynamics of a diverse rodent assemblage in mixed grass-shrub habitat, southeastern Colorado, 1995-2000. J. Wildl. Dis. 41:12-28, 2005.

Calisher, C.H., Root, J.J., Mills, J.N., Rowe, J.E., Reeder, S.A., Jentes, E.S., Wagoner, K. and Beaty, B.J. Epizootiology of Sin Nombre and El Moro Canyon hantaviruses, southeastern Colorado, 1995-2000. J. Wildl. Dis. 41:1-11, 2005.

Kuenzi, A. J., R. J. Douglass, C. W. Bond, C. H. Calisher, and J. N. Mills. Long-term dynamics of Sin Nombre viral RNA and antibody in deer mice in Montana. J. Wildl. Dis. 41:473-481, 2005.

Douglass, R.J., Calisher, C.H., and Bradley, K.C. State-by-state incidences of hantavirus pulmonary syndrome in the United States, 1993-2004. Vector-Borne Zoon. Dis., 5:189-192, 2005.

Doty, J.B., Calisher, C.H., Root, J.J., and Beaty, B.J. Microhabitat use by deer mice in response to fluctuations in pinyon mouse abundance (accepted, Intermountain Journal of Science)

Douglass, R.J., Calisher C.H., Wagoner K., and Mills, J.N. Sin Nombre virus infection of deer mice in Montana: characteristics of newly infected mice, incidence, and temporal pattern of infection. J. Wildl. Dis.43:XXX-YYY, 2007.

Calisher, C.H., Wagoner K.D., Amman B.R., Root J., Douglass, R.J. Kuenzi, A.J., Abbott, K.D., Parmenter, C., Yates, T.L., Ksiazek T.G., Beaty, B.J., and Mills, J.N. Demographic factors associated with prevalence of antibody to Sin Nombre virus in deer mice in the western United States. J. Wildl. Dis. 43: XXX-XXX, 2007.

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