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At least 19 recordsLinked to original sources
PubMed2025

Molecular Evolution and Zoonotic Potential of Muju Virus (Orthohantavirus puumalaense) in Craseomys regulus, Republic of Korea.

Orthohantavirus puumalaense causes hemorrhagic fever with renal syndrome in Europe, with Puumala virus (PUUV) as its primary representative. Muju virus (MUJV), harbored by Craseomys regulus, an Arvicolinae rodent species endemic to the Republic of Korea (ROK), is also a genotype of O. puumalaense. However, their genomic diversity and zoonotic potential remain largely unknown. To investigate their prevalence, 185 voles were collected from 23 regions of the ROK between 2012 and 2023. Serological assays detected anti-PUUV immunoglobulin G antibodies in five samples (3.1%), whereas reverse-transcription polymerase chain reaction confirmed MUJV RNA in identical specimens (2.7%). Amplicon-based nanopore sequencing facilitates near-complete genome recovery, enabling high-resolution comparative analysis. Phylogenetic analysis revealed distinct genetic lineages in Gangwon and Jeollabuk Provinces. Evolutionary rate estimates indicated greater sequence divergence in the S and L segments than in the M segment. A zoonotic risk assessment revealed that most MUJV variants exhibited moderate-to-high spillover potential. The molecular detection of MUJV in Cheorwon, Gangwon Province, expands its known geographic range and provides the first molecular evidence of MUJV circulation in this region. These findings highlight the need for continued surveillance and seroprevalence studies of MUJV to assess its potential for human exposure and public health relevance in the ROK.

Animals↗
PubMed2025

Lanka virus, a Mus booduga-borne orthohantavirus infection-associated febrile illness in Sri Lanka.

BACKGROUND: In Sri Lanka, a high seroprevalence of antibodies against hantaviruses was reported in communities affected by chronic kidney disease of unknown etiology (CKDu). Recently, two rodent-borne hantaviruses, Lanka virus and Anjozorobe virus, were identified in these areas. However, it is unclear which virus is the source of infection in humans, and its pathogenicity is unknown. METHODOLOGY/PRINCIPAL FINDINGS: A total of 181 sera from febrile patients from two CKDu-endemic regions, Girandurukotte and Polonnaruwa, were examined and Lanka virus genome was detected in two IgM-positive febrile patients. Of 76 serum samples from patients with fever of unknown etiology collected during 2016 examined to identify hantavirus genomes, antibodies, and serotypes, 10 were IgG-positive with five of them having IgM also. They were all without clinical features of hemorrhagic fever with renal syndrome, but three patients required treatment in the intensive care unit. A serotyping strategy was established based on the antigenic difference of the glycoprotein Gn of Lanka and Anjozorobe viruses. Using this method, febrile patients were found to be infected with the Lanka virus and none of the patient sera showed Anjozorobe virus infection pattern. Additionally, a total of 373 previously diagnosed seropositive serum samples from CKDu patients and healthy residents were serotyped to categorize 87% of seropositives as Lanka virus infection. CONCLUSIONS/SIGNIFICANCE: Lanka virus carried by little Indian field mouse (Mus booduga) is transmitted to humans, likely causing febrile illness occasionally while leading to severe disease in some of the febrile patients.

Humans↗
PubMed2026

Host hybridization enabled the emergence of a reassorted hantavirus lineage.

The exchange of genetic material between individuals is a key driver of evolution and diversification across most branches of life. Segmented viruses can exchange genetic material through reassortment of genomic segments. New viral strains that emerge from reassortments can have greater infection ranges and higher virulence, although concrete examples of the adaptive advantages of reassortants in nature apart from influenza remain rare. We studied here the evolutionary history and consequences of reassortment in Tula orthohantavirus (TULV) in a hybrid zone between evolutionary lineages of its reservoir host, the common vole (Microtus arvalis). Across 58 trapping sites and 127 infected voles, we detected 27 TULV reassortants in a 12.5 km broad zone at the contact of the parental TULV clades, resembling a viral hybrid zone concordant with the hosts'. Phylogenomic analyses revealed three independent reassortment events, but most of the host hybrid zone was dominated by a single strain with a reassorted M-Segment, which encodes the surface glycoprotein. We detected clade-specific variation in the glycoprotein's N-terminal region consisting of five residues, two of which showed evidence of positive selection. In silico 3D modeling of seven glycoproteins confirmed that this N-terminal region has a unique and specific structure for each TULV clade and the dominant reassortants and is the only structurally variable region of the TULV glycoprotein. Our findings suggest that reassortment between the parental TULV clades in the contact region has resulted in a transgressive virus phenotype potentially adapted to hybrid hosts. This demonstrates the potential of zones of hybridization for the emergence of new virus strains with novel evolutionary trajectories.

Animals↗
PubMed2026

RNA Virus Diversity, Cross-Species Transmission, and Molecular Constraints in Two Closely Related Rat Species.

Viral infection involves co-evolution with hosts, yet the molecular determinants that constrain viral cross-species transmission remain poorly understood. Here, we established conspecific and heterospecific co-housing models for two closely related rat species, Rattus norvegicus (RN) and Rattus tanezumi (RT), both maintained in laboratory settings for over 10 generations, together with wild-caught RT individuals. Using meta-transcriptomic sequencing and population genomic analyses, we compared their RNA virus profiles and investigated the potential molecular constraints on cross-species viral transmission. From 63 rats, we characterized an extensive RNA virome comprising more than 600 viruses, including 7 zoonotic viruses, 29 viruses with cross-species transmission potential, and 335 novel viruses. Notably, the prevalence of Seoul orthohantavirus (SEOV) was significantly higher in RN than in RT. Population genomic analysis revealed that RN exhibited higher heterozygosity in Itgb3 (the gene encoding the SEOV receptor, β3-integrin) and Tlr7 (the gene encoding the receptor for viral ssRNA, Toll-like receptor 7) compared to RT. These genetic variations likely represent the molecular determinants responsible for the differential susceptibility to SEOV between the two species. Our findings clarify the diversity and prevalence of RNA viruses in closely related rodent species and highlight host genetic barriers that may influence zoonotic spillover risk.

Animals↗
PubMed2025

Phylogenetic diversity and molecular evolution of Hantaan virus harbored by Apodemus chejuensis on Jeju Island, Republic of Korea, 2022-2023.

BACKGROUND: Hantaan virus (HTNV), hosted by Apodemus spp., is a well-recognized causative agent of hemorrhagic fever with renal syndrome (HFRS) and poses a crucial global public health concern. Based on the current evidence, HTNV carried by A. chejuensis is proposed as the likely etiological agent of HFRS on Jeju Island, Republic of Korea (ROK). METHODOLOGY/PRINCIPAL FINDINGS: In this study, 50 small mammals were collected from five locations in Seogwipo-si and Jeju-si on Jeju Island, ROK, during 2022-2023. Serological and molecular analyses revealed HTNV prevalence rates of 34% (16/47) and 27.7% (13/47), respectively. Using a multiplex polymerase chain reaction-based nanopore sequencing approach, nine complete HTNV genomes were sequenced from the lung tissues of A. chejuensis, representing the first comprehensive genomic characterization of HTNV from Seogwipo-si (Hogeun-dong) and Jeju-si (Sangdae-ri). Phylodynamic analyses suggest evolutionary divergence and phylogeographic diversity, with four unique amino acid substitutions identified in HTNV genomes from Seogwipo-si. CONCLUSION/SIGNIFICANCE: This study provides important insights into the genomic surveillance, genetic diversity, and evolutionary dynamics of orthohantaviruses, which are essential for guiding effective public health strategies to control and prevent future HFRS outbreaks in the ROK.

Animals↗
PubMed1996

Immune responses to inactivated vaccine in people naturally infected with hantaviruses.

An inactivated Hantaan virus vaccine for hemorrhagic fever with renal syndrome (HFRS) was given by injection to 15 people who were naturally infected with either Hantaan or Seoul viruses. Immunofluorescent antibody (IFA), reversed passive hemagglutination inhibition (RPHI), hemagglutination inhibition (HI), and neutralization antibody (NA) assays were used to measure the antibody titers of the vaccinated people before and after three doses of vaccine. The results indicated that IFA and RPHI antibody titers were boosted significantly (P < 0.05) after the vaccination. Either Hantaan or Seoul virus could induce two-way cross-reactive neutralization antibody responses in humans. After HTNV vaccine immunization, the NA titers of people with natural infection increased significantly (P < 0.05) to both Hantaan and Seoul viruses, while the relative dominance between these two type responses was still similar to that of natural infection. It is worthwhile to studying the procedure further to inoculate two different virus vaccines for improving the cross-protective effect.

Adolescent↗
PubMed1996

Hantavirus S RNA sequence from a fatal case of HPS in New York.

In April, 1995, the second fatal case of hantavirus pulmonary syndrome (HPS) occurred in the northeast in a New York State resident. Using the patient's lung tissue obtained at autopsy, the S genomic RNA segment of a hantavirus, designated H-NY1, was amplified by reverse transcriptase-polymerase chain reaction (RT-PCR), cloned, and sequenced. The S RNA was found to contain 2084 nucleotides, 6 nucleotides longer than reported by Hjelle et al. (1995) for the virus associated with the first northeastern case (RI-1). There were 101 nucleotide differences in the S RNA between the H-NY1 and RI-1, which result in the prediction of a single amino-acid change in the nucleocapsid (N) protein. Rodents were trapped for serologic and virologic studies at the patient's residence and work site. The white-footed mouse (Peromyscus leucopus) was the most frequently captured species and more than 50% of those trapped near the patient's residence showed serologic evidence of hantavirus infection. Using RT-PCR it was possible to amplify hantavirus S RNA sequence from the lung tissues of 8 out of 11 seropositive animals. No difference in nucleotide sequence was found between the HPS patient sequence and the P. leucopus sequence (nucleotides 189 to 599). These data are consistent with those of Hjelle et al. (1995) in suggesting that P. leucopus is the primary rodent vector for the etiologic agent of HPS in the northeastern United States.

Adult↗
PubMed1997

The first human isolate of Puumala virus in Scandinavia as cultured from phytohemagglutinin stimulated leucocytes.

A virus isolate was recovered from blood leucocytes of a patient with nephropathia epidemica (NE). Leucocytes were isolated from EDTA-blood by dextran sedimentation and cultured on monolayers of Vero E6 cells in the presence of phytohemagglutinin (PHA) in roller tubes during the first 72 hours of incubation followed by rolling culture for three weeks in total. Thereafter the first subculture was done in a plastic flask and afterward at at least 6 week intervals. Antigen was first detected after 6 months and 2 weeks of culture. When tested by monoclonal antibodies and patient sera the isolate had the characteristics of a PUU virus. PCR amplification using PUU-specific primers and subsequent partial sequencing of the S and M segments revealed that the Umeå/305/human/95 virus differs from the Finnish PUU Sotkamo rodent prototype virus and is similar but not identical to rodent strains of PUU virus acquired from the same region as the patient isolate. It is we concluded that the first human isolate of the etiologic agent of NE in Scandinavia was recovered from blood leucocytes stimulated with PHA by long-term culture in Vero E6 cells. The isolate belongs to the PUU serotype of hantaviruses as shown by its serologic profile and partial sequencing data.

Adult↗
PubMed1997

Puumala virus and two genetic variants of Tula virus are present in Austrian rodents.

Puumala and Tula viruses are hantaviruses found in Europe and are associated with the rodents Clethrionomys glareolus and Microtus arvalis, respectively. Puumala virus is associated with the human disease nephropathia epidemica. In Austria, ten clinically diagnosed cases of nephropathia epidemica, presumably caused by Puumala virus infection, have been reported but not virologically confirmed [Leschinskaya et al., 1991; Aberle et al., 1996]. To identify the hantaviruses that are present in Austria, five species of rodents were trapped and screened for virus antibodies, antigen, and RNA. Hantaviruses were detected in two species, Cl. glareolus and M. arvalis, by reverse transcription-polymerase chain reaction (RT-PCR). RT-PCR products from Cl. glareolus tissues yielded a unique Puumala virus sequence distinct from Puumala virus sequences reported from other parts of Europe. RT-PCR products from M. arvalis tissues yielded two genetically distinct Tula virus sequences, one similar to sequences reported from Slovakia and the Czech Republic and another that appears to be a novel genetic variant of Tula virus. This is the first confirmed report of hantaviruses in Austria.

Animals↗
PubMed1998

Retrospective serological and genetic study of the distribution of hantaviruses in Greece.

A retrospective serological and genetic study of hantaviruses responsible for hemorrhagic fever with renal syndrome (HFRS) in Greece during the last 17 years is presented. Fifty-one serum samples taken from 30 HFRS cases previously diagnosed by immunofluorescence assay were tested by ELISA for IgG (Hantaan, Dobrava, and Puumala) and IgM antibodies (Hantaan and Puumala). Results were compatible with the majority of infections being related to hantaviruses carried by rodents of the subfamily Murinae. RNA was extracted from 26 selected samples and reverse transcriptase-polymerase chain reaction (RT-PCR) was performed using primers specifically designed for the detection of hanta-viruses associated with murine (MS-N-specific, MM-G1-specific primers) or arvicoline rodents (PPT-N-specific primers). In addition, primers previously designed for the detection of the G2 coding region of the Murine-associated hanta-viruses were also used. Sequencing of the PCR products was then performed, followed by phylogenetic analysis of nucleotide sequence differences. Eleven out of the 26 serum samples tested were found to be positive by PCR with the MS-N primers, whereas four were positive with the MM-G1 primers, and only two with the G2 primers. None of the samples was found positive with the PPT primers. The sequence analysis showed that the virus that was responsible for these 11 HFRS cases was the Dobrava virus, which is endemic throughout the Balkans.

Adult↗
PubMed1999

Analysis of puumala hantavirus genome in patients with nephropathia epidemica and rodent carriers from the sites of infection.

Reverse transcription-polymerase chain reaction (RT-PCR) followed by sequence and phylogenetic analyses were used to study specimens from nine Finnish nephropathia epidemica (NE) patients admitted to hospital during the epidemic in winter 1996-1997. Blood samples from six patients were found to be positive for the partial M- and/or S-segment sequences of Puumala hantavirus (PUUV). Analyses of these sequences (nt 2168-2610 for the M segment, and nt 819-1082 for the S segment) revealed six distinct PUUV strains showing highest similarity to previously described PUUV strains from Finland: 90-95% for the S segment, and 90-99% for the M segment. Accordingly, on the phylogenetic trees calculated for both viral segments, all six human strains were placed within the Finnish genetic lineage of PUUV. Attempts were made to trace five RT-PCR-positive patients to local bank voles (Clethrionomys glareolus) infected with wild-type PUUV, and for two patients a comparative analysis of human- and rodent-originated viral sequences was undertaken. Whereas in the first case the differences between the sequences were substantial (5. 7% for the S segment, and 10.8%, for the M segment), in the other case the M segment sequence recovered from the clinical specimen was 100% identical to three sequences recovered from rodent lungs, and the S sequences differed by one silent substitution only. This is the first finding of virtually identical PUUV sequences in an NE patient and a natural rodent host from the site of infection.

Adolescent↗
PubMed1999

Genetic investigation of novel hantaviruses causing fatal HPS in Brazil.

Although hantavirus pulmonary syndrome (HPS) was discovered in North America in 1993, more recent investigations have shown that the disease is a much larger problem in South America, where a greater number of cases and HPS-associated viruses have now been detected. Here we describe the genetic investigation of three fatal HPS cases from Brazil, including a 1995 case in Castelo dos Sonhos (CAS) in the state of Mato Grosso and two 1996 cases in the counties of Araraquara (ARA) and Franca (FRA), in the state of São Paulo. Reverse transcription-polymerase chain reaction (RT-PCR) products representing fragments of the hantavirus N, G1, and G2 coding regions were amplified from patient acute-phase serum samples, and the nucleotide (nt) sequences (394, 259, and 139 nt, respectively) revealed high deduced amino acid sequence identity between ARA and FRA viruses (99.2%, 96.5%, and 100%, respectively). However, amino acid differences of up to 14.0% were observed when ARA and FRA virus sequences were compared with those of the geographically more distant CAS virus. Analysis of a 643-nt N coding region and a 1734-nt predominantly G2-encoding region of ARA and CAS virus genomes confirmed that these Brazilian viruses were distinct and monophyletic with previously characterized Argentinean hantaviruses, and suggested that Laguna Negra (LN) virus from Paraguay was ancestral to both the Brazilian and Argentinean viruses. The phylogenetic tree based on the N coding fragment also placed LN in a separate clade with Rio Mamore virus from Bolivia. At the amino acid level, ARA and CAS viruses appeared more closely related to the Argentinean viruses than they were to each other. Similarly, analysis of the diagnostic 139-nt G2 fragment showed that the Juquitiba virus detected in a 1993 fatal HPS case close to São Paulo city, Brazil was closer to Argentinean viruses than to ARA or CAS viruses. These data indicate that at least three different hantavirus genetic lineages are associated with Brazilian HPS cases.

Antibodies, Viral↗
PubMed2000

Transmission of Black Creek Canal virus between cotton rats.

Black Creek Canal (BCC) virus is a hantavirus associated with hantavirus pulmonary syndrome in southeastern North America. The virus was isolated from the spleen of a cotton rat (Sigmodon hispidus) trapped in southern Florida. Our previous studies have shown that we could consistently infect male cotton rats with BCC virus in the laboratory. These animals became persistently infected and virus could be detected in salivary glands, urine, and feces. In this report we show: (1) female and male cotton rats are equally susceptible to BCC virus infection, (2) susceptibility to infection was not influenced by age, (3) all inoculated rats transmitted the infection to uninoculated cage mates, and (4) offspring of infected rats became infected despite the presence of high maternal antibodies. The course of BCC virus infection, as determined by antibody response and the ability to isolate or detect virus, appeared to be similar regardless of whether the rats obtained their infection by inoculation or contact with inoculated rats. J. Med. Virol. 60:70-76, 2000. Published 2000 Wiley-Liss, Inc.

Animals↗
PubMed2000

Hantavirus infection in Taiwan: the experience of a geographically unique area.

Hantaviruses are rodent-borne viruses, and they, mainly the Hantaan (HTN) serotype, are the causative agents of a group of febrile nephropathies known as "hemorrhagic fever with renal syndrome (HFRS). " Despite the fact that HFRS is frequently reported in China, with an annual incidence of 50,000-100,000 cases, one puzzling observation that no local case of HFRS has been confirmed in Taiwan has yet to be explained. We hypothesized that the hantavirus strain prevailing in Taiwan mainly belongs to the mild strain, the Seoul (SEO) strain, and the absence of severe disease was related to the absence of HTN. To test these hypotheses, this epidemiologic study was performed, including a seroprevalence survey and phylogenetic analysis on hantavirus isolated from the rodent population trapped in major seaports, rural, and mountainous areas of Taiwan. This study also included rodents and viruses from two isolated islands, Kinmen and Matzu, which are geographically adjacent to the east coast of mainland China. There were a total of 5,461 rodents of 16 species captured, and R. norvegicus was the most common species, with an antibody prevalence much higher in international seaports (20%) than in rural regions (approximately 5%) and intermediate in some domestic seaports. By reverse transcriptase polymerase chain reaction (RT-PCR), 33.9% of the seropositive R. norvegicus were found to have amplifiable hantavirus sequences in their lung tissues, and subsequent phylogenetic analyses indicated that almost all hantavirus in Taiwan was most closely related to the prototype SEO strain, and no HTN strain was recovered from any rodent species indigenous to Taiwan. The seroprevalence of SEO infection in R. norvegicus on Kinmen and Matzu was also different from that in southern provinces of China but closely resembled that in seaports in Taiwan, and the SEO identified was genetically linked to Taiwanese SEO strains. These results substantiate our hypotheses, and suggest that the epidemiology of hantavirus infection in Taiwan are different from that in China, where the HTN and SEO strains and HFRS concurrently prevail.

Animals↗
PubMed2000

A neutralizing recombinant human antibody Fab fragment against Puumala hantavirus.

A combinatorial human antibody Fab pComb3H library, generated from splenic lymphocytes of a Puumala hantavirus (PUUV) immune individual, was selected against PUUV using the phage display technique. Panning was carried out with antigens immobilized by MAbs directed to the two PUUV envelope glycoproteins G1 and G2. Thirteen Fabs, with reactivity directed to PUUV and specifically the G2 protein, as assessed by immunofluorescence and ELISA respectively, were isolated in crude preparations. By a focus reduction neutralization test (FRNT), four of the 13 crude Fab preparations exhibited type-specific neutralization of PUUV (strain Sotkamo) with 44-54% reduction in the number of foci. After affinity purification, the four Fab clones exhibited 50% focus reduction of PUUV at concentrations below 2 microg/ml. Sequencing of the heavy and light chain complementarity determining regions (CDR) 1-3 showed that the four selected clones were identical within the antibody binding regions. In inhibition tests with the PUUV G2-specific MAbs, 4G2 and 1C9, a new epitope important for neutralization, designated as G2-a3, was defined. This epitope, overlapping partially the neutralizing epitope recognized by the human MAb 1C9, seems to be unique for the PUUV serotype since none of the Fab clones neutralized any of the other hantaviruses tested.

Amino Acid Sequence↗
PubMed2006

Nitric oxide and peroxynitrite have different antiviral effects against hantavirus replication and free mature virions.

Reactive nitrogen intermediates (RNI), like nitric oxide (NO) and peroxynitrite, have antiviral effects against certain viruses. Hantaviruses, like other members of the Bunyaviridae family, have previously not been shown to be sensitive to RNI. In this study, we compared the effects of NO and peroxynitrite on hantavirus replication and free mature virions in vitro, and of inducible nitric oxide synthase (iNOS) in hantavirus-infected suckling mice. The NO-generating compound S-nitroso-N-acetylpenicillamine (SNAP), as well as cytokine-induced NO, strongly inhibited hantavirus replication in Vero E6 cells, while pretreatment of free virions with SNAP only had a limited effect on their viability. In contrast, 3-morpholinosydnonimine hydrochloride (SIN-1), a peroxynitrite donor, inhibited virus replication only to a very low extent in vitro, but pretreatment of virus with SIN-1 led to a considerably lowered viability of the virions. Infections of various human cell types per se did not induce NO production. The viral titers in iNOS(-/-) mice were higher compared to the controls, suggesting that NO inhibits hantavirus replication in vivo. In conclusion, we show that NO has strong antiviral effects on hantavirus replication, and peryoxynitrite on mature free virions, suggesting that different RNI can have different effects on various parts of the replication cycle for the same virus.

Animals↗
PubMed2002

Hantaviruses in Estonia.

Human serum samples collected from healthy individuals in 14 counties were screened by ELISA in order to investigate the presence of hantavirus infections in Estonia. Out of 1,234 serum samples, 124 were found positive for hantavirus-specific IgG and were subsequently serotyped by a focus reduction neutralization test. A total of 112 samples neutralized at least one of the examined hantaviruses-Puumala (PUUV), Saaremaa (SAAV), Dobrava (DOBV), Hantaan, and Seoul viruses-and thereby, the focus reduction neutralization test confirmed the overall hantavirus seroprevalence rate in Estonia to be 9.1%. Most of the sera showed a specific reaction (at least 4-fold higher endpoint titer) of neutralizing antibodies to PUUV (5.1%), while 3.4% showed a SAAV- or SAAV/DOBV-specific reaction. The fact that seven sera (0.6%) could not be serotyped may indicate the presence of an unknown hantavirus serotype. Hantavirus infections were confirmed in 13 of 14 investigated counties, with highly varying seroprevalence rates (1.0-28.4%). The sex ratio was 1.8:1.0 (M:F), and the antibody prevalence peaked in the age group 45-54 years. A total of 513 rodents of seven species trapped in seven counties were examined for the presence of hantavirus antigen, in order to study the distribution of hantavirus natural carriers. Two species, Clethrionomys glareolus and Apodemus agrarius, were found positive for hantaviral antigen in 13.7% and 4.5% of the investigated rodents, respectively. Analyses of viral sequences recovered from infected C. glareolus tissue samples showed that the infecting virus belonged to the PUUV genotype, confirming that PUUV circulates in mainland Estonia. The Estonian PUUV strains were placed in the closest proximity to Russian PUUV strains in phylogenetic trees, suggesting a common evolutionary history. Together with earlier data on SAAV in A. agrarius, the results revealed that two hantaviruses, PUUV and SAAV, are common in Estonia and that the incidence of human infection is high in both cases.

Animals↗