scholarly journals Serological survey of Seewis virus antibodies in patients suspected for hantavirus infection in Finland; a cross-reaction between Puumala virus antiserum with Seewis virus N protein?

2015 ◽  
Vol 96 (7) ◽  
pp. 1664-1675 ◽  
Author(s):  
Jiaxin Ling ◽  
Anne Jääskeläinen ◽  
Satu Hepojoki ◽  
Jussi Hepojoki ◽  
Heikki Henttonen ◽  
...  
Keyword(s):  
Cross Reaction ◽  
Hantavirus Infection ◽  
Puumala Virus ◽  
Serological Survey ◽  
N Protein

scholarly journals Flash-Like Albuminuria in Acute Kidney Injury Caused by Puumala Hantavirus Infection

Pathogens ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 615
Author(s):  
Paula Mantula ◽  
Johanna Tietäväinen ◽  
Jan Clement ◽  
Onni Niemelä ◽  
Ilkka Pörsti ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Acute Phase ◽  
Kidney Injury ◽  
University Hospital ◽  
Hantavirus Infection ◽  
Puumala Virus ◽  
Disappearance Rate ◽  
Time Points ◽  
Albumin Excretion ◽  
Fever Onset

Transient proteinuria and acute kidney injury (AKI) are characteristics of Puumala virus (PUUV) infection. Albuminuria peaks around the fifth day and associates with AKI severity. To evaluate albuminuria disappearance rate, we quantified albumin excretion at different time points after the fever onset. The study included 141 consecutive patients hospitalized due to acute PUUV infection in Tampere University Hospital, Finland. Timed overnight albumin excretion (cU-Alb) was measured during the acute phase in 133 patients, once or twice during the convalescent phase within three months in 94 patients, and at six months in 36 patients. During hospitalization, 30% of the patients had moderately increased albuminuria (cU-Alb 20–200 μg/min), while 57% presented with severely increased albuminuria (cU-Alb >200 μg/min). Median cU-Alb was 311 μg/min (range 2.2–6460) ≤7 days after fever onset, 235 μg/min (range 6.8–5479) at 8–13 days and 2.8 μg/min (range 0.5–18.2) at 14–20 days. After that, only one of the measurements showed albuminuria (35.4 μg/min at day 44). At six months, the median cU-Alb was 2.0 μg/min (range 0.6–14.5). Albuminuria makes a flash-like appearance in PUUV infection and returns rapidly to normal levels within 2–3 weeks after fever onset. In the case of AKI, this is a unique phenomenon.

scholarly journals Expression of the Nucleoprotein of the Puumala Virus from the Recombinant Semliki Forest Virus Replicon: Characterization and Use as a Potential Diagnostic Tool

2003 ◽  
Vol 10 (4) ◽  
pp. 658-663 ◽  
Author(s):  
A. Billecocq ◽  
D. Coudrier ◽  
F. Boué ◽  
B. Combes ◽  
H. Zeller ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Semliki Forest Virus ◽  
Immunoglobulin M ◽  
Enzyme Linked Immunosorbent Assay ◽  
Puumala Virus ◽  
Wild Rodents ◽  
Serological Tests ◽  
N Protein ◽  
Antigenic Properties ◽  
Native Antigen

ABSTRACT Puumala virus (Bunyaviridae family, Hantavirus genus) causes a mild form of hemorrhagic fever with renal syndrome (HFRS) called nephropathia epidemica in northern and central Europe. Serological tests are used for diagnosis, but antigen production is difficult because the virus grows poorly in tissue culture. We expressed the N protein (nucleoprotein) of Puumala virus via the Semliki Forest virus (SFV) replicon in mammalian cells and compared its antigenic properties with those of the native antigen derived from Puumala virus-infected cells. Detection of immunoglobulin G or immunoglobulin M by enzyme-linked immunosorbent assay (ELISA), μ-capture ELISA, and indirect immunofluorescence assay was (at least) as effective with the recombinant antigen as with the native antigen when HFRS patient sera or organ washes from wild rodents were tested. No nonspecific reaction was observed. Thus, the SFV-expressed N protein of Puumala virus appears as a valid antigen, specific and sensitive for serological investigations.

scholarly journals Occurrence of Immunoglobulin M Antibodies against Several Bacterial and Viral Pathogens in Acute Hantavirus Infection

2012 ◽  
Vol 19 (9) ◽  
pp. 1549-1551
Author(s):  
Nele Wellinghausen ◽  
Andrea Goetz ◽  
Ursula Weber
Keyword(s):  
Epstein Barr Virus ◽  
Immunoglobulin M ◽  
Hantavirus Infection ◽  
Puumala Virus ◽  
Virus Infections ◽  
Viral Pathogens ◽  
Content Type ◽  
Barr Virus ◽  
Epstein Barr ◽  
Type Gene

ABSTRACTElevated levels of immunoglobulin M antibodies against various pathogens, most frequently Epstein-Barr-virus andCoxiella burnetii, were detected by immunoassay in 15 of 48 patients (31.3%) with acute Puumala virus infections. Although the mechanisms leading to this IgM response are not clear yet, polyspecific immunoglobulin M antibodies have to be taken into account to avoid misinterpretation of serological results in acute hantavirus infection.

scholarly journals Hantavirus infection-induced B cell activation elevates free light chains levels in circulation

2021 ◽  
Vol 17 (8) ◽  
pp. e1009843
Author(s):  
Jussi Hepojoki ◽  
Luz E. Cabrera ◽  
Satu Hepojoki ◽  
Carla Bellomo ◽  
Lauri Kareinen ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Cell Clone ◽  
Light Chains ◽  
Hantavirus Infection ◽  
Puumala Virus ◽  
B Cell Activation ◽  
Free Light Chains

In humans, orthohantaviruses can cause hemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). An earlier study reported that acute Andes virus HPS caused a massive and transient elevation in the number of circulating plasmablasts with specificity towards both viral and host antigens suggestive of polyclonal B cell activation. Immunoglobulins (Igs), produced by different B cell populations, comprise heavy and light chains; however, a certain amount of free light chains (FLCs) is constantly present in serum. Upregulation of FLCs, especially clonal species, associates with renal pathogenesis by fibril or deposit formations affecting the glomeruli, induction of epithelial cell disorders, or cast formation in the tubular network. We report that acute orthohantavirus infection increases the level of Ig FLCs in serum of both HFRS and HPS patients, and that the increase correlates with the severity of acute kidney injury in HFRS. The fact that the kappa to lambda FLC ratio in the sera of HFRS and HPS patients remained within the normal range suggests polyclonal B cell activation rather than proliferation of a single B cell clone. HFRS patients demonstrated increased urinary excretion of FLCs, and we found plasma cell infiltration in archival patient kidney biopsies that we speculate to contribute to the observed FLC excreta. Analysis of hospitalized HFRS patients’ peripheral blood mononuclear cells showed elevated plasmablast levels, a fraction of which stained positive for Puumala virus antigen. Furthermore, B cells isolated from healthy donors were susceptible to Puumala virus in vitro, and the virus infection induced increased production of Igs and FLCs. The findings propose that hantaviruses directly activate B cells, and that the ensuing intense production of polyclonal Igs and FLCs may contribute to acute hantavirus infection-associated pathological findings.

scholarly journals Patterns of Puumala virus infection in Finland

2003 ◽  
Vol 8 (1) ◽  
pp. 9-13 ◽  
Author(s):  
Angie Rose ◽  
O Vapalahti ◽  
O Lyytikäinen ◽  
P Nuorti
Keyword(s):  
Infectious Disease ◽  
Geographic Region ◽  
Hantavirus Infection ◽  
Puumala Virus ◽  
National Surveillance ◽  
Virus Infections ◽  
Common Cause ◽  
Disease Register ◽  
Epidemic Period ◽  
Puumala Virus Infection

Puumala hantavirus infection is prevalent throughout most of Europe, and in endemic areas it may be the most common cause of acute renal failure. To evaluate trends in incidence of Puumala virus infections in Finland, we analysed national surveillance data in 12-month periods from March 1995 to February 2002. During this time, 8184 laboratory-confirmed cases were notified to the National Infectious Disease Register. Three epidemic periods were identified, for which the number of cases was more than 1400 (there were approximately 600-900 cases per non-epidemic period). The incidence of Puumala hantavirus infection varied by geographic region during the study period, and the overall number of cases may be increasing.

scholarly journals Hantavirus RdRp Requires a Host Cell Factor for Cap Snatching

2018 ◽  
Vol 93 (5) ◽  
Author(s):  
Subbiah Jeeva ◽  
Sheema Mir ◽  
Adrain Velasquez ◽  
Brandy A. Weathers ◽  
Aljona Leka ◽  
...  
Keyword(s):  
Host Cell ◽  
Virus Replication ◽  
Umbilical Vein ◽  
Hemorrhagic Fever ◽  
Hantavirus Infection ◽  
Early Event ◽  
N Protein ◽  
Host Cell Factor ◽  
Endonuclease Domain

ABSTRACTThe hantavirus RNA-dependent RNA polymerase (RdRp) snatches 5′ capped mRNA fragments from the host cell transcripts and uses them as primers to initiate transcription and replication of the viral genome in the cytoplasm of infected cells. Hantavirus nucleocapsid protein (N protein) binds to the 5′ caps of host cell mRNA and protects them from the attack of cellular decapping machinery. N protein rescues long capped mRNA fragments in cellular P bodies that are later processed by an unknown mechanism to generate 10- to 14-nucleotide-long capped RNA primers with a 3′ G residue. Hantavirus RdRp has an N-terminal endonuclease domain and a C-terminal uncharacterized domain that harbors a binding site for the N protein. The purified endonuclease domain of RdRp nonspecifically degraded RNAin vitro. It is puzzling how such nonspecific endonuclease activity generates primers of appropriate length and specificity during cap snatching. We fused the N-terminal endonuclease domain with the C-terminal uncharacterized domain of the RdRp. The resulting NC mutant, with the assistance of N protein, generated capped primers of appropriate length and specificity from a test mRNA in cells. Bacterially expressed and purified NC mutant and N protein required further incubation with the lysates of human umbilical vein endothelial cells (HUVECs) for the specific endonucleolytic cleavage of a test mRNA to generate capped primers of appropriate length and defined 3′ terminusin vitro. Our results suggest that an unknown host cell factor facilitates the interaction between N protein and NC mutant and brings the N protein-bound capped RNA fragments in close proximity to the endonuclease domain of the RdRp for specific cleavage at a precise length from the 5′ cap. These studies provide critical insights into the cap-snatching mechanism of cytoplasmic viruses and have revealed potential new targets for their therapeutic intervention.IMPORTANCEHumans acquire hantavirus infection by the inhalation of aerosolized excreta of infected rodent hosts. Hantavirus infections cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS), with mortality rates of 15% and 50%, respectively (1). Annually 150,000 to 200,000 cases of hantavirus infections are reported worldwide, for which there is no treatment at present. Cap snatching is an early event in the initiation of virus replication in infected hosts. Interruption in cap snatching will inhibit virus replication and will likely improve the prognosis of the hantavirus disease. Our studies provide mechanistic insight into the cap-snatching mechanism and demonstrate the requirement of a host cell factor for successful cap snatching. Identification of this host cell factor will reveal a novel therapeutic target for combating this viral illness.

scholarly journals Serosurvey of hantavirus infection in humans in the border region between Brazil and Argentina

2011 ◽  
Vol 44 (2) ◽  
pp. 131-135 ◽  
Author(s):  
William Marciel de Souza ◽  
Alex Martins Machado ◽  
Luiz Tadeu Moraes Figueiredo ◽  
Everton Boff
Keyword(s):  
Immunofluorescence Assay ◽  
Farm Workers ◽  
Border Region ◽  
Hantavirus Pulmonary Syndrome ◽  
Hantavirus Infection ◽  
Western Region ◽  
Igg Antibodies ◽  
Farm Worker ◽  
Indirect Contact ◽  
N Protein

INTRODUCTION: According to reports by the Ministry of Health, in the far western region of the State of Santa Catarina, there have been no reports of hantavirus pulmonary syndrome, a zoonotic disease transmitted by feces of infected rodents. A seroepidemiological study of residents of this region, was conducted, with the aim of determining the presence of hantavirus infections. A total of 340 volunteers of both genus, from the towns of Belmonte and Paraíso, were studied. METHODS: The serum of these patients was collected and used to detect IgG antibodies against recombinant N protein of Araraquara hantavirus, by ELISA assay. The positive samples were then titrated and confirmed by immunofluorescence assay. RESULTS: This study demonstrated the presence of IgG antibodies against hantavirus N protein in 3.5% of the population. The most frequent occupation was farm worker, 81% had direct and indirect contact with rodents, 91.7% of positive cases were farm workers, indicating that the probable cause of infection occurred during barn cleaning. These antibodies are noteworthy, given that the levels of antibodies were verified in individuals whose contact with hantavirus may have occurred many years ago. CONCLUSIONS: This study shows the circulation of hantavirus in the region, a fact that until now, had not reported. All the serum reagents had contact with the pathogen, but did not develop pulmonary and cardiovascular syndrome. It is important to remain alert, because hantavirus is a serious and emerging disease of some relevance.

scholarly journals Long-lived Memory T Lymphocyte Responses After Hantavirus Infection

2002 ◽  
Vol 196 (5) ◽  
pp. 579-588 ◽  
Author(s):  
Heather L. Van Epps ◽  
Masanori Terajima ◽  
Jukka Mustonen ◽  
T. Petteri Arstila ◽  
Elizabeth A. Corey ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Acute Infection ◽  
Public Health Problem ◽  
T Cell Response ◽  
Hantavirus Infection ◽  
Important Public Health Problem ◽  
Virus Persistence ◽  
Ctl Epitopes ◽  
N Protein ◽  
Ctl Responses

Puumala virus (PUUV) is a hantavirus that causes hemorrhagic fever with renal syndrome (HFRS), which is an important public health problem in large parts of Europe. We examined the memory cytolytic T lymphocyte (CTL) responses in 13 Finnish individuals who had HFRS between 1984 and 1995. In seven of these donors, we detected virus-specific CTL responses against the PUUV nucleocapsid (N) protein after in vitro stimulation with PUUV. Six novel CD8+ CTL epitopes were defined on the N protein and were found to be restricted by various HLA alleles including A2, A28, B7, and B8. This is the first demonstration of PUUV-specific CTL responses in humans, and the first identification of CTL epitopes on PUUV. In addition, this study provides one of the few characterizations of a human antiviral memory T cell response, without the complicating issues of virus persistence or reinfection. Interferon (IFN)-γ ELISPOT analysis showed that memory CTL specific for these epitopes were present at high frequency in PUUV-immune individuals many years after acute infection in the absence of detectable viral RNA. The frequencies of PUUV-specific CTL were comparable to or exceeded those found in other viral systems including influenza, EBV and HIV, in which CTL responses may be boosted by periodic reinfection or virus persistence.

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