Direct Genetic Detection of Dobrav a Virus in Greek and Albanian Patients with Hemorrhagic Fever with Renal Syndrome

Ántoniadis, Antonis; Stylianakis, Antonis; Papa, Anna; Alexiou-Daniel, S.; Lampropoulos, Alexis; Nichol, Stuart T.; Peters, C. J.; Spiropoulou, Christina F.

doi:10.1093/infdis/174.2.407

Cited by 83 publications

(53 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Dobrava Virus (Dobv) Is a Hantavirus That Causes Hemorrhagicmentioning

confidence: 99%

“…A direct proof for DOBV-Af strains as an etiologic agent of HFRS was established by amplification of DOBV-Af nucleotide sequences from HFRS patients in Greece, Albania, and Croatia (1,25,33). HFRS cases caused by DOBV infection in South-East Europe were found to be clinically moderate or even severe with a case fatality index of up to 12% (1,3,22,33).In Central Europe, DOBV RNA has been predominantly detected in a different mouse species, the striped field mouse (A. agrarius). Phylogenetic analysis of these viral sequences from A. agrarius led to the definition of a second genetic DOBV clade, 50,51).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Central European Dobrava Hantavirus Isolate from a Striped Field Mouse ( Apodemus agrarius )

et al. 2005

View full text Add to dashboard Cite

Dobrava virus (DOBV) is a hantavirus that causes hemorrhagic fever with renal syndrome (HFRS) inEurope. It is hosted by at least two rodent species, Apodemus flavicollis and A. agrarius. According to their natural hosts they form the distinct genetic lineages DOBV-Af and DOBV-Aa, respectively. We have now established a DOBV isolate named Slovakia (SK/Aa) from an A. agrarius animal captured in Slovakia. The complete S and M and partial L segment nucleotide sequences of the new isolate were determined. Phylogenetic analyses showed that the SK/Aa isolate clustered together with the other DOBV-Aa sequences amplified from A. agrarius before and can be taken as the representative of this genetic lineage. SK/Aa, in comparison with a DOBV-Af isolate, was used for serotyping neutralizing antibodies of HFRS patients in Central Europe. Most patients' sera exhibited a higher endpoint titer when probed with our new isolate, suggesting that DOBV-Aa strains are responsible for most of the DOBV-caused HFRS cases in this region.Hantaviruses represent a unique genus Hantavirus within the Bunyaviridae family. They are "emerging viruses" that cause two human zoonoses: hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome. The virus genome consists of three segments of negative-stranded RNA; the large (L) segment encodes the viral RNA-dependent RNA polymerase, the medium (M) segment the glycoprotein precursor (GPC), and the small (S) segment of the nucleocapsid (N) protein. In contrast to other genera of the Bunyaviridae family, hantaviruses are not transmitted by arthropods. Instead, they are spread by aerosolized rodent excreta and produce a chronic infection with no apparent harm in their natural hosts, rodents of the family Muridae (18,28,45,46). In Europe, at least two hantaviruses, Dobrava virus (DOBV) and Puumala virus (PUUV), are known to be pathogenic for humans (for reviews, see references 18 and 37). In addition, a single case of renal syndrome with pulmonary involvement has been very recently associated with infection by Tula virus (14). Currently, DOBV is intensively studied because of its unique properties; different virus lineages exist in different regions of Europe, and these lineages are harbored by different host reservoirs and probably display different levels of virulence in humans.A viable DOBV strain was isolated from lungs of a yellownecked mouse (Apodemus flavicollis) captured in a natural focus of HFRS in Dobrava village, Slovenia, South-East Europe (5). This virus isolate represents the DOBV prototype strain (named Slovenia or Slo/Af here) from A. flavicollis. Moreover, a second DOBV cell culture isolate (Ano-Poroia or AP/Af) has been established from an A. flavicollis mouse trapped in Greece (32, 34). Molecular phylogenetic analyses of nucleotide sequences from these cell culture-derived virus isolates, as well as from further South-East European A. flavicollis-associated strains, demonstrated their close mutual relationship (2, 4, 34, 35). These strains form a unique A. fla...

show abstract

Section: Dobrava Virus (Dobv) Is a Hantavirus That Causes Hemorrhagicmentioning

confidence: 99%

mentioning

confidence: 99%

Central European Dobrava Hantavirus Isolate from a Striped Field Mouse ( Apodemus agrarius )

et al. 2005

View full text Add to dashboard Cite

show abstract

“…2 An association of DOB virus with HFRS was recently found in patients from southeastern Europe (Albania, Greece, former Yugoslavia) and Russia. [5][6][7] In a study performed in Estonia (northeastern Europe), Plyusnin and others 8 demonstrated the presence of DOB virus in A. agrarius, the natural host of HTN virus in Asia. 1,2 In Slovakia (central Europe), HFRS is a well-known disease; clinical cases as well as infected rodents have been serologically diagnosed using HTN or PUU virus antigens.…”

mentioning

confidence: 98%

Short report: simultaneous occurrence of Dobrava, Puumala, and Tula Hantaviruses in Slovakia.

Sibold

Meisel²,

Lundkvist³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

Abstract. The prevalence of antibody to hantaviruses in Slovakia (serum panel n ϭ 2,133) was lower in the western part (0.54%) and higher in the eastern part (1.91%) of the country and was found to be significantly enhanced in a group of forest workers from eastern Slovakia (5.88%). One-third of the IgM-negative convalescent phase sera from patients with hemorrhagic fever with renal syndrome exhibited antibodies reacting predominantly with Puumala virus antigen, while two-thirds had antibodies directed mainly against Hantaan virus antigen. Fine analysis of two Hantaan virus-reactive sera by a focus reduction neutralization test showed that Dobrava hantavirus was the source of these human infections. Initial results of rodent screening indicated the circulation of Dobrava virus in populations of striped field mice (Apodemus agrarius) in eastern Slovakia.

show abstract

“…Puumala hantavirus (PUUV) causes a milder form of HFRS named nephropathia epidemica (NE), which occurs in northern and central Europe. The more severe forms of HFRS are caused by Hantaan (Asia) and Dobrava (Europe) viruses, while Seoul virus (worldwide) causes an intermediate form (3,17). Hantaviruses are carried by specific rodent hosts, and virus transmission to humans occurs via inhalation of aerosolized animal excreta (5, 32).…”

mentioning

confidence: 99%

Wild-Type Puumala Hantavirus Infection Induces Cytokines, C-Reactive Protein, Creatinine, and Nitric Oxide in Cynomolgus Macaques

Klingström

Plyusnin

Vaheri

et al. 2002

J Virol

View full text Add to dashboard Cite

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.Hantaviruses, members of the family Bunyaviridae, are known to cause two serious and often fatal human diseases: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). The clinical symptoms of HFRS are characterized by fever, thrombocytopenia, renal failure, and, in severe cases, hemorrhage caused by capillary leak syndrome (13, 31). Puumala hantavirus (PUUV) causes a milder form of HFRS named nephropathia epidemica (NE), which occurs in northern and central Europe. The more severe forms of HFRS are caused by Hantaan (Asia) and Dobrava (Europe) viruses, while Seoul virus (worldwide) causes an intermediate form (3,17). Hantaviruses are carried by specific rodent hosts, and virus transmission to humans occurs via inhalation of aerosolized animal excreta (5, 32). The mortality of HFRS varies between Ͻ0.1 and 12%, depending on the causative virus (31, 32). Sin Nombre virus, Andes virus, and related hantaviruses cause HPS in the Americas, mainly characterized by acute respiratory dysfunction and with a mortality rate of approximately 40% (26, 27).In the rodent reservoirs, hantaviruses cause persistent and subclinical infections (31). Although successfully used, e.g., for studies of immune responses and for evaluation of vaccine candidates and/or therapeutic reagents, rodent models are of limited value for studying the pathogenesis of human hantavirus infections. Only two earlier studies of nonhuman primates have been reported, and both described models with certain limitations (9, 40). We have previously shown phenotypic and genetic changes of PUUV when propagated in cell culture, resulting in a decrease of infectivity for its natural host, the bank vole (Clethrionomys glareolus) (22). We therefore speculated that wild-type PUUV (strain Kazan-wt) might infect nonhuman primates in a way different from previously reported studies. Here we report the first successful experimental infection of cynomolgus macaque...

show abstract

Direct Genetic Detection of Dobrav a Virus in Greek and Albanian Patients with Hemorrhagic Fever with Renal Syndrome

Cited by 83 publications

References 14 publications

Central European Dobrava Hantavirus Isolate from a Striped Field Mouse ( Apodemus agrarius )

Central European Dobrava Hantavirus Isolate from a Striped Field Mouse ( Apodemus agrarius )

Short report: simultaneous occurrence of Dobrava, Puumala, and Tula Hantaviruses in Slovakia.

Wild-Type Puumala Hantavirus Infection Induces Cytokines, C-Reactive Protein, Creatinine, and Nitric Oxide in Cynomolgus Macaques

Contact Info

Product

Resources

About