EFFECTS OF IMMUNOSUPPRESSION ON WEST NILE VIRUS INFECTION IN HAMSTERS

ROSA MATEO Department of Pathology, Department of Internal Medicine and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas

Search for other papers by ROSA MATEO in
Current site
Google Scholar
PubMed
Close
,
SHU-YUAN XIAO Department of Pathology, Department of Internal Medicine and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas

Search for other papers by SHU-YUAN XIAO in
Current site
Google Scholar
PubMed
Close
,
HILDA GUZMAN Department of Pathology, Department of Internal Medicine and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas

Search for other papers by HILDA GUZMAN in
Current site
Google Scholar
PubMed
Close
,
HAO LEI Department of Pathology, Department of Internal Medicine and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas

Search for other papers by HAO LEI in
Current site
Google Scholar
PubMed
Close
,
AMELIA P. A. TRAVASSOS DA ROSA Department of Pathology, Department of Internal Medicine and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas

Search for other papers by AMELIA P. A. TRAVASSOS DA ROSA in
Current site
Google Scholar
PubMed
Close
, and
ROBERT B. TESH Department of Pathology, Department of Internal Medicine and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas

Search for other papers by ROBERT B. TESH in
Current site
Google Scholar
PubMed
Close
Restricted access

A research study, comparing the pathogenesis of experimental West Nile virus (WNV) infection in immunocompetent and immunosuppressed golden hamsters, is described. Cyclophosphamide was used to immunosuppress the animals. The immunosuppressed hamsters had a prolonged period of viremia, depressed humoral immune response, more extensive and severe pathology, and higher fatality rate than the untreated immunocompetent animals. Histopathological and immunohistochemical studies of tissues from the two groups showed that pathologic changes in the untreated infected animals were confined to the brain and spinal cord, whereas the histopathological changes and WNV antigen distribution in the immunosuppressed animals were much more extensive and diffuse, involving the adrenal, kidney, heart and lung, and brain and spinal cord. Results of this study in the hamster model provide insight into the increased severity of WNV infection observed in immunosuppressed people.

Author Notes

Reprint requests: Robert B. Tesh, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0609, E-mail: rtesh@utmb.edu.
  • 1

    Nash D, Mostashari F, Fine A, Miller J, O’Leary D, Murray K, Huang A, Rosenberg A, Greenburg A, Sherman M, Wong S, Layton M, Campbell GL, Roehrig JT, Gubler DJ, Shieh WJ, Zaki S, Smith P, 2001. The outbreak of West Nile virus infection in the New York City area in 1999. N Engl J Med 344 :1807–1814.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Available at http://www.cdc.gov/ncidod/dvbid/westnile/surv&controlCaseCount04_detailed.htm. Accessed February 28, 2005.

    • PubMed
    • Export Citation
  • 3

    Mostashari F, Bunning ML, Kitsutani PT, Singer DA, Nash D, Cooper MJ, Katz N, Liljebjelke KA, Biggerstaff BJ, Fine AD, Layton MC, Mullin SM, Johnson AJ, Martin DA, Hayes EB, Campbell GL, 2001. Epidemic West Nile encephalitis, New York, 1999: Results of a household-based seroepidemiological survey. Lancet 358 :261–264.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Campbell GL, Marfin AA, Lanciotti RS, Gubler DJ, 2002. West Nile virus. Lancet Infect Dis 2 :519–529.

  • 5

    Petersen LR, Marfin AA, 2002. West Nile virus: A primer for the clinician. Ann Intern Med 137 :173–179.

  • 6

    Granwehr BP, Lillibridge KM, Higgs S, Mason PW, Aronson JF, Campbell GA, Barrett ADT, 2004. West Nile virus: Where are we now? Lancet Infect Dis 4 :547–556.

  • 7

    Iwamoto M, Jernigan DB, Guasch A, Trepka MJ, Blackmore CG, Hellinger WC, Pham SM, Zaki S, Lanciotti RS, Lance-Parker SE, Diaz Granados CA, Winquist AG, Perlino CA, Wiersma S, Hillyer KL, Goodman JL, Marfin AA, Chamberland ME, Peterson LR, 2003. Transmission of West Nile virus from an organ donor to four transplant recipients. N Engl J Med 348 :2196–2203.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Ravinddra KV, Freifeld AG, Kalil AC, Mercer DF, Grant WJ, Botha JF, Wrenshall LE, Stevens RB, 2004. West Nile virus-associated encephalitis in recipients of renal and pancreas transplants: Case series and literature review. Clin Infect Dis 38 :1257–1260.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Solomon T, Fisher AF, Beasley DWC, Mandava P, Granwehr BP, Langsjoen H, Travassos da Rosa APA, Barrett ADT, Tesh RB, 2003. Natural and nosocomial infection in a patient with West Nile encephalitis and extrapyramidal movement disorders. Clin Infect Dis 36 :e140–e145.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Huang C, Slater B, Rudd R, Parchuri N, Hull R, Dupuis M, Hindenburg A, 2002. First isolation of West Nile virus from a patient with encephalitis in the United States. Emerg Infect Dis 8 :1367–1371.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Hong DS, Jacobson KL, Raad II, de Lima M, Anderlini P, Fuller GN, Ippoliti C, Cool RM, Leeds NE, Narvios A, Han XY, Padula A, Champlin RE, Hosing C, 2003. West Nile encephalitis in 2 hematopoietic stem cell transplant recipients: Case series and literature review. Clin Infect Dis 37 :1044–1049.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    DeSalvo D, Roy-Chaudhury P, Peddi R, Merchen T, Konijetti K, Gupta M, Boardman R, Rogers C, Buell J, Hanaway M, Broderick J, Smith R, Woodle ES, 2004. West Nile virus encephalitis in organ transplant recipients: Another high risk-group for meningoencephalitis and death. Transplantation 77 :466–469.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Xiao SY, Guzman H, Zhang H, Travassos da Rosa AP, Tesh RB, 2001. West Nile virus infection in the golden hamster (Mesocricetus auratus): A model for West Nile encephalitis. Emerg Infect Dis 7 :714–721.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Semenov BF, Vargin VV, Zschiesche W, Veckenstedt A, 1975. Influence of certain immunodepressants on experimental Flavivirus and enterovirus infections in mice. Intervirology 5 :22–24.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Tonry JH, Xiao SY, Siirin M, Chen H, Travassos da Rosa APA, Tesh RB, 2005. Persistent shedding of West Nile virus in urine of experimentally infected hamsters. Am J Trop Med Hyg 72 :320–324.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Beaty BJ, Calisher CH, Shope RE, 1989 Arboviruses. Schmidt NJ, Emmons RW, eds. Diagnostic Procedures for Viral, Rickettsial and Chlamydial infections. Sixth edition. Washington, DC: American Public Health Association, 797–856.

    • PubMed
    • Export Citation
  • 17

    Sbrana E, Tonry JH, Xiao SY, Travassos da Rosa APA, Higgs S, Tesh RB, 2005. Oral transmission of West Nile virus in a hamster model. Am J Trop Med Hyg 72 :325–329.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Ahmed AR, Hombal SM, 1984. Cyclophosphamide (Cytoxan*). J Am Acad Dermatol 11 :1115–1126.

  • 19

    Chambers TJ, Diamond MS, 2003. Pathogenesis of flavivirus encephalitis. Adv Virus Res 60 :273–342.

  • 20

    Wang T, Fikrig E, 2004. Immunity to West Nile virus. Curr Opin Immunol 16 :519–523.

  • 21

    Cole GA, Nathanson N, 1968. Potentiation of experimental arbovirus encephalitis by immunosuppressive doses of cyclophosphamide. Nature 220 :399–401.

  • 22

    Camenga DL, Nathanson N, Cole GA, 1974. Cyclophosphamide-potentiated West Nile viral encephalitis: Relative influence of cellular and humoral factors. J Infect Dis 130 :634–641.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Nathanson N, Cole GA, 1970. Immunosuppression and experimental virus infection of the nervous system. Adv Virus Res 16 :397–448.

  • 24

    Thind IS, Price WH, 1969. The effect of cyclophosphamide treatment on experimental arbovirus infections. Amer J Epid 90 :62–68.

  • 25

    Nathanson N, Cole GA, 1970. Fatal Japanese encephalitis virus infection in immunosuppressed spider monkeys. Clin Exp Immunol 6 :161–166.

  • 26

    Bradish CJ, Allner K, Fitzgeorge R, 1975. Immunomodification and the expression of virulence in mice by defined strains of Semliki Forest virus: The effects of cyclophosphamide. J Gen Virol 28 :225–237.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Fitzgeorge R, Bradish CJ, 1980. Differentiation of strains of yellow fever virus in γ-irradiated mice. J Gen Virol 50 :345–356.

  • 28

    Penn RG, Guarner J, Sejvar JJ, Hartman H, McComb RD, Nevins DL, Bhatnagar J, Zaki SR, 2006. Persistent neuroinvasive West Nile virus infection in an immunocomprimised patient. Clin Infect Dis 42 :680–683.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Guarner J, Shieh WJ, Hunter S, Paddock CD, Morken T, Campbell GL, Marfin AA, Zaki SR, 2004. Clinicopathologic study and laboratory diagnosis of 23 cases with West Nile virus encephalomyelitis. Hum Pathol 35 :983–990.

    • PubMed
    • Search Google Scholar
    • Export Citation
Past two years Past Year Past 30 Days
Abstract Views 124 124 19
Full Text Views 513 6 0
PDF Downloads 75 2 0
 
Membership Banner
 
 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save