Biomedical subjects

J Klingström

Publications and source records attributed to J Klingström.

6 recordsLinked to original sources

PubMed2004

Delayed viremia and antibody responses in Puumala hantavirus challenged passively immunized cynomolgus macaques.

No specific therapy is currently available against hemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome. In order to study if passive immunization could inhibit hantavirus infection and/or symptoms, we inoculated two cynomolgus macaques with neutralizing monoclonal antibodies and subsequently challenged them with wild-type Puumala virus (PUUV), recently shown to induce typical signs of milder HFRS in cynomolgus macaques. Although viral load and antibody titers did not differ substantially as compared to the two control monkeys, a delayed onset of viremia and seroconversion was observed in the immunized monkeys. Interestingly, one of the immunized monkeys showed no symptoms, nor elevated of levels of IL-6, IL-10, and TNF-alpha, while the other developed severe symptoms and elevated levels of those cytokines, believed to be involved in PUUV-pathogenesis.

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PubMed2003

Genetic immunization is augmented by murine polyomavirus VP1 pseudocapsids.

To improve immune responses induced by DNA immunization, murine polyomavirus major capsid protein (VP1) pseudocapsids were complexed with a DNA plasmid encoding the p37 (p24 and p17) nucleocapsid proteins of the human immunodeficiency virus type 1 (HIV-1). A 10-fold increase in antibody titer was noted in mice given DNA plasmid together with VP1 pseudocapsids in comparison to animals that received DNA plasmid alone. Cell mediated responses to HIV-1 p24 occurred, but were not significantly augmented by delivering the DNA as a VP1 complex. We have consequently for the first time shown a carrier/adjuvant effect of polyomavirus pseudocapsids that strongly increased the humoral immune response in DNA immunization.

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PubMed2002

Rodent host specificity of European hantaviruses: evidence of Puumala virus interspecific spillover.

In order to investigate rodent host specificity of European hantaviruses, experimental infection of colonized and wild-trapped rodents was performed. In addition to the natural rodent reservoir, Clethrionomys glareolus, Puumala hantavirus (PUUV) could infect colonized Microtus agrestis and Lemmus sibiricus, but not Syrian hamsters or Balb/C mice. Neither C. glareolus, nor M. agrestis, could be readily infected by Tula hantavirus (TULV). Wild-trapped Apodemus flavicollis and A. agrarius, the natural reservoirs of Dobrava (DOBV) and Saaremaa (SAAV) hantaviruses, respectively, could both be infected by SAAV. NMRI mice could also be infected by SAAV, but with lower efficiency as compared to Apodemus mice. Balb/C and NMRI laboratory mice, but not C. glareolus, could be infected by DOBV. To our knowledge, this is the first time DOBV and SAAV have been shown to infect adult laboratory mice. Moreover, potential hantavirus spillover infections were investigated in wild-trapped rodents. In addition to the natural host C. glareolus, we also found M. arvalis and A. sylvaticus with a history of PUUV infection. We did not find any C. glareolus or A. sylvaticus infected with TULV, a hantavirus which is known to circulate in the same geographical regions of Belgium.

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PubMed2002

Distribution of hantavirus foci in Belgium.

During 1999 and 2000, we performed rodent captures on 15 sites all over Belgium to evaluate the presence of hantaviruses in local rodent populations. Viral antibody and RNA detection was performed by ELISA/focus reduction neutralisation test and RT-PCR, respectively. We found hantavirus-positive rodents on 13 out of 15 trapping sites and 3 rodent species were found positive for hantavirus infection. Apart from Puumala virus that was carried by Clethrionomys glareolus, 2 additional rodent species, Microtus arvalis and Apodemus sylvaticus, were found antibody- and/or RNA-positive.

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PubMed2002

Tula hantavirus in Belgium.

European common voles (Microtus arvalis), captured in Belgium in 1999, were proven by molecular as well as by serological techniques to be infected with Tula hantavirus (TULV). This is the first evidence for the presence of TULV in this country. No indication of spill-over infections of Puumala virus, known to be highly endemic among bank voles (Clethrionomys glareolus) within the same geographical regions as the trapped TULV-infected common voles, was observed. Together with previous reports on the circulation of TULV in eastern/central Europe, this finding suggests a more wide-spread circulation of this hantavirus serotype throughout the continent.

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PubMed2002

Wild-type Puumala hantavirus infection induces cytokines, C-reactive protein, creatinine, and nitric oxide in cynomolgus macaques.

Hantaviruses cause two severe human diseases: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Approximately 200,000 cases are reported annually, and there is to date no specific treatment available. A major obstacle in studying the medical aspects of HFRS and HPS has been the lack of an adequate animal model. Here we show that infection of cynomolgus macaques by wild-type Puumala hantavirus resulted in typical signs of HFRS including lethargy, anorexia, proteinuria, and/or hematuria, in addition to cytokine (interleukin 6 [IL-6], IL-10, and tumor necrosis factor alpha), C-reactive protein, creatinine, and nitric oxide responses. Viral RNA was detected in plasma from days 3 to 7 postinoculation until days 24 to 28 postinoculation, infectious virus was recovered, and the virus-specific immune responses (immunoglobulin M [IgM], IgG, and neutralizing antibodies) mimicked those seen in humans. The results indicated that the monkey model will provide a valuable tool for studies of pathogenesis, candidate vaccines, and antivirals for hantavirus disease.

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