Development of Novel Immunoglobulin G (IgG), IgA, and IgM Enzyme Immunoassays Based on Recombinant Puumala and Dobrava Hantavirus Nucleocapsid Proteins

Meisel, Helga; Wolbert, Anne; Ražanskienė, Aušra; Marg, Andreas; Kazāks, Andris; Sasnauskas, Kęstutis; Pauli, Georg; Ulrich, Rainer G.; Krüger, Detlev H.

doi:10.1128/cvi.00208-06

Cited by 51 publications

(41 citation statements)

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“…Due to the hazardous nature of hantaviruses and a short-term viremia in hantavirus-infected individuals, diagnosis of HFRS is usually based on serology [33]. The main limitation of serology is cross-reactivity, which often complicates interpretation of results, especially in areas where multiple hantaviruses cocirculate [34].…”

Section: Discussionmentioning

confidence: 99%

Clinical and virological characteristics of hantavirus infections in a 2014 Croatian outbreak

Vilibić-Čavlek

Furic²,

Barbić

et al. 2017

J Infect Dev Ctries

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Introduction: Croatia is endemic for hemorrhagic fever with renal syndrome (HFRS), with both Puumala (PUUV) and Dobrava virus (DOBV) documented. Several large outbreaks were recorded in 1995, 2002, and 2012. We analyzed demographic, clinical, laboratory, and virological characteristics of HFRS cases detected in three geographically close natural foci (Ogulin, Slunj, and the Plitvice Lakes surroundings) during the 2014 outbreak. Methodology: From January to December 2014, 122 patients with suspected HFRS were tested for hantavirus IgM/IgG antibodies using an indirect immunofluorescence assay (IFA). Cross-reactive samples were further tested using a western blot (WB). For hospitalized patients from Ogulin area, clinical and laboratory data were analyzed. Results: Acute infection was documented in 57 (46.7%) patients, of whom 75.4% were hospitalized. Ten (8.2%) patients were found to be IgG seropositive. Patients were 15-69 years of age and predominantly male (74.5%). The outbreak started in winter months, with most cases recorded from May to July (80.7%). The most frequently reported symptoms were fever (96.3%), chills/shivering (62.9%), and lumbar pain (48.1%). Mild clinical form was found in 66.7% patients, moderate in 18.5%, and severe in 14.8% patients (all but one infected with PUUV). One patient died. Using IFA, 48.8% patients showed monotypic antibody response, while in 51.2%, cross-reactive antibodies were found. PUUV was confirmed in 94.7% and DOBV in 5.3% HFRS cases by WB. Conclusions: Central mountainous Croatian regions are still highly endemic areas for HFRS. A higher percentage of severe PUUV infections could be at least partly associated with a patient's immune status.

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Section: Discussionmentioning

confidence: 99%

Clinical and virological characteristics of hantavirus infections in a 2014 Croatian outbreak

Vilibić-Čavlek

Furic²,

Barbić

et al. 2017

J Infect Dev Ctries

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“…IgG and IgM ELISA was performed using recombinant nucleocapsid protein of PUUV, DOBV, and HTNV as described previously (12). Titers of 1:400 or more were considered positive.…”

Section: Methodsmentioning

confidence: 99%

“…In only few cases was the IgM response found to be delayed. IgM disappears within months; however, when using sensitive test formats, it can be detected in single cases as late as 2 years after the acute phase of infection (8,12). The IgG response is long lasting but sometimes delayed; in about 10% of acute-phase, IgM-positive sera, no IgG can be found with routine assays (8,20).…”

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Hantavirus Disease Outbreak in Germany: Limitations of Routine Serological Diagnostics and Clustering of Virus Sequences of Human and Rodent Origin

et al. 2007

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In Europe, hemorrhagic fever with renal syndrome results mainly from infection with Puumala virus (PUUV) or Dobrava virus. For 31 patients from a hantavirus disease outbreak in Lower Bavaria, a district in southeast Germany, serodiagnosis was undertaken by enzyme-linked immunosorbent assay, immunofluorescence assay, and immunoblot analysis. In a few of these cases, however, PUUV-specific typing of antibodies by these standard assays failed and a virus neutralization assay under biosafety level 3 conditions was required to verify the infection by this virus type. PUUV RNA was amplified by reverse transcription-PCR from acute-phase sera of three patients and was found to be very closely related to virus sequences obtained from bank voles (Clethrionomys glareolus) trapped in the same area. These findings link the outbreak with a novel PUUV lineage, "Bavaria," circulating in the local rodent population. The Bavaria lineage associated with the outbreak is only distantly related to other PUUV lineages from Germany.

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“…Schmidt and coworkers (31) investigated the cross-reactivity of rabbit sera raised against the N proteins of SEOV and other hantaviruses. The N-protein-specific antibodies induced by natural infection in human and experimental infections and immunizations have been found to be highly cross-reactive among the different hantaviruses (16,26,31). The N-protein-specific antibody titers in SEOV N-protein-immunized rabbits were only slightly lower than those in rabbits immunized with the N protein of the closely related HTNV and much lower than those in rabbits immunized with the N proteins of PUUV, SNV, and ANDV.…”

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confidence: 95%

Use of Saccharomyces cerevisiae -Expressed Recombinant Nucleocapsid Protein To Detect Hantaan Virus-Specific Immunoglobulin G (IgG) and IgM in Oral Fluid

Petraityte¹,

Li²,

Hunjan³

et al. 2007

Clin Vaccine Immunol

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Hantaan virus (HTNV) is the prototype species of the genus Hantavirus and has remained the epidemiologically most important species in the genus until now. Hantaviruses form a separate genus within the family Bunyaviridae, forming a group of closely related negative-stranded RNA viruses (4,17,25,29). Hantaviruses are the causative agents of hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome. HFRS occurs mainly in Europe and Asia and is associated with HTNV, Seoul virus (SEOV), Dobrava virus (DOBV), and Puumala virus (PUUV) infections (34). Usually, hantavirus pulmonary syndrome is found in the New World, where most of the cases are caused by the Sin Nombre virus (SNV) and Andes virus (ANDV) serotypes (8,11,15). Hantaviruses are transmitted to humans through the aerosol excreta of infected small mammals, mainly wild rodents (17). In China, HTNV together with SEOV accounts for at least 100,000 cases of hantavirus-associated HFRS each year. Approximately 150,000 HFRS cases occur annually worldwide. HTNV infection is characterized by fever, renal dysfunction, and in some cases, hemorrhagic manifestations (9,10,12,13,15).Hantaviruses have a tripartite genome that encodes a nucleocapsid protein (N protein), two envelope glycoproteins, and a viral RNA polymerase (30). The viral N protein elicits a strong humoral immune response in infected patients and immunized animals and has been extensively used to produce reagents for the diagnosis of hantavirus infections (1, 14, 21). Comparison of the amino acid sequences of five amino-terminal immunogenic regions of the N proteins of the HTNV, SEOV, and DOBV hantaviruses shows that they have high degrees of homology. Rabbit polyclonal sera produced against cell culture-grown virus and recombinant viral proteins were tested for their responses to five hantavirus antigens. Two types of antibody responses were generated; hence, two groups of sera could be distinguished, with HTNV, SEOV, and DOBV be attributed to the first group and SNV and PUUV to the second group (3). Schmidt and coworkers (31) investigated the cross-reactivity of rabbit sera raised against the N proteins of SEOV and other hantaviruses. The N-protein-specific antibodies induced by natural infection in human and experimental infections and immunizations have been found to be highly cross-reactive among the different hantaviruses (16,26,31). The N-protein-specific antibody titers in SEOV N-protein-immunized rabbits were only slightly lower than those in rabbits immunized with the N protein of the closely related HTNV and much lower than those in rabbits immunized with the N proteins of PUUV, SNV, and ANDV. Similarly, the anti-

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Development of Novel Immunoglobulin G (IgG), IgA, and IgM Enzyme Immunoassays Based on Recombinant Puumala and Dobrava Hantavirus Nucleocapsid Proteins

Abstract: Human infections with Asian and European hantaviruses can result in hemorrhagic fever

Cited by 51 publications

References 59 publications

Clinical and virological characteristics of hantavirus infections in a 2014 Croatian outbreak

Clinical and virological characteristics of hantavirus infections in a 2014 Croatian outbreak

Hantavirus Disease Outbreak in Germany: Limitations of Routine Serological Diagnostics and Clustering of Virus Sequences of Human and Rodent Origin

Use of Saccharomyces cerevisiae -Expressed Recombinant Nucleocapsid Protein To Detect Hantaan Virus-Specific Immunoglobulin G (IgG) and IgM in Oral Fluid

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