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At least 19 recordsLinked to original sources
PubMed1987

Effects of human and murine interferons against hemorrhagic fever with renal syndrome (HFRS) virus (Hantaan virus).

The effects of human interferons (IFN-alpha, IFN-beta, IFN-gamma) on the replication of Hantaan virus (HV) in Vero E6 cells were examined. Pretreatment of cells with human IFNs resulted in dose-dependent inhibition of HV plaque formation. Of the 3 human IFNs, IFN-beta inhibited virus replication most effectively. Pretreatment of murine macrophage cells with mouse IFN-beta also resulted in an inhibition of viral growth and then the effect of murine IFN-beta in newborn ICR mice infected with HV was also examined. When newborn mice were inoculated intraperitoneally with HV, their survival rate was approximately 20%. When they were treated with interferon 6 h before infection with virus, their survival rate was 85-90%. When IFN and virus were injected simultaneously into the intraperitoneal cavity, the survival rate of the mice was also higher than that of untreated mice. When the mice were treated with IFN for 2 or 7 consecutive days after infection, their survival rate was 70%. These results suggest that IFN may be effective for both prophylactic and therapeutic purposes in Hantaan virus infection.

Animals↗
PubMed2005

Immunogenicity of combination DNA vaccines for Rift Valley fever virus, tick-borne encephalitis virus, Hantaan virus, and Crimean Congo hemorrhagic fever virus.

DNA vaccines for Rift Valley fever virus (RVFV), Crimean Congo hemorrhagic fever virus (CCHFV), tick-borne encephalitis virus (TBEV), and Hantaan virus (HTNV), were tested in mice alone or in various combinations. The bunyavirus vaccines (RVFV, CCHFV, and HTNV) expressed Gn and Gc genes, and the flavivirus vaccine (TBEV) expressed the preM and E genes. All vaccines were delivered by gene gun. The TBEV DNA vaccine and the RVFV DNA vaccine elicited similar levels of antibodies and protected mice from challenge when delivered alone or in combination with other DNAs. Although in general, the HTNV and CCHFV DNA vaccines were not very immunogenic in mice, there were no major differences in performance when given alone or in combination with the other vaccines.

Animals↗
PubMed1986

Coding strategy of the S genome segment of Hantaan virus.

Hantaan virus is the type species of the recently recognized Hantavirus genus of Bunyaviridae. The small (S) RNA segment of the negative-sense, tripartite genome was molecularly cloned and the nucleotide sequence was determined. The RNA sequence derived from the cDNA copy was found to contain 1696 nucleotides. A single open reading frame of sufficient size to encode the virus nucleocapsid protein was detected in the cDNA corresponding to viral complementary-sense RNA. RNA transcripts of the cDNA were synthesized with SP6 polymerase and were used to program cell-free reticulocyte lysate translation systems. Viral complementary-sense transcripts served as efficient messages in translation systems and generated Hantaan nucleocapsid protein. No translation products were detected when lysates were programmed with viral-sense transcripts. This coding assignment of the nucleocapsid protein to the viral complementary-sense RNA of the S genome segment is consistent with those of other members of this family. Unlike other Bunyaviridae, which encode both a nucleocapsid protein and a nonstructural (NSs) protein of similar sizes, a NSs protein has not been identified for Hantaan virus. Furthermore, other than the nucleocapsid protein gene sequence, the only potential open reading frame in Hantaan S RNA encoded a short, 48-amino acid polypeptide which initiated two codons beyond the termination of the nucleocapsid protein in the same reading frame. These data demonstrate that the coding strategy of the Hantaan virus S RNA is different than those reported for other viruses in this family.

Amino Acid Sequence↗
PubMed2003

Prevalence of rabies virus and Hantaan virus infections in commensal rodents and shrews trapped in Bangkok.

Five hundred rodents and shrews (Rattus norvegicus: 458, Rattus rattus: 28, Rattus exulans: 5, Mus musculus: 4 and Suncus murine: 5) trapped from the fresh food markets around Bangkok area were investigated for rabies virus and Hantaan virus infections. No rabies viral antigens in the animals' brains were detected by direct immunofluorescence. On the other hand, antibodies to Hantaan virus were demonstrated in the sera of 7 (1.53%) R. norvegicus caught in various markets using a particle agglutination technique. Further determination of the viral genome in rat lung tissue was performed by reverse transcriptase-polymerase chain reaction (RT-PCR) and nested PCR, 3 (0.66%) out of 7 were positive. HindIII and HifI restriction enzyme analyses showed the pattern of the Hantaan virus genome in 2 samples and that of the Seoul virus genome in the other. The results of the present study suggest that rodents from Bangkok's fresh food markets did not carry rabies. Thus, getting rid of rabies in dogs or cats in the Bangkok area may be easier than anticipated because there are no sources of asymptomatic reservoirs. This may result in the low incidence of rabies patients observed in Bangkok. On the contrary, the presence of antibodies and the Hantaan virus genome and Seoul virus genome in R. norvegicus will definitely provide evidence for physicians to be aware of hemorrhagic fever with renal syndrome (HFRS) and other clinical settings of Hantaan/Seoul virus disease in patients with a history of having contact with rats or their excreta.

Animals↗
PubMed1995

A vaccinia virus-vectored Hantaan virus vaccine protects hamsters from challenge with Hantaan and Seoul viruses but not Puumala virus.

To investigate the ability of a vaccinia virus-vectored vaccine expressing the M and the S segments of Hantaan (HTN) virus (C. S. Schmaljohn, S. E. Hasty, and J. M. Dalrymple, Vaccine 10:10-13, 1992) to elicit a protective immune response against other hantaviruses, we vaccinated hamsters with the recombinant vaccine and challenged them with HTN, Seoul (SEO), or Puumala (PUU) virus. Neutralizing antibodies to HTN virus were found in all vaccinated hamsters both before and after challenge. Neutralizing antibody titers to SEO virus were present at low levels or were undetectable after two immunizations with the vaccine but were positive in all vaccinated hamsters after challenge with SEO virus and were also positive in control animals that were not challenged. Neutralizing antibodies to PUU virus were observed only in hamsters previously challenged with PUU virus. To assay for virus in the blood and tissues of the hamsters, we developed a nested reverse transcriptase (RT)-PCR with cross-reactive outer primers and serotype-specific inner primers. The RT-PCR specifically detected as little as 1 PFU of virus in serum containing high-titer neutralizing antibodies and was more sensitive than immunofluorescent antibody staining for detecting virus in lung and kidney specimens of infected hamsters. By using the RT-PCR, we found that vaccinated hamsters, challenged with HTN or SEO virus, neither were viremic nor had evidence of virus in their lungs or kidneys. In contrast, vaccinated hamsters challenged with PUU virus were viremic and had PUU virus-specific nucleic acid in their organs.

Animals↗
PubMed2006

A pseudotype vesicular stomatitis virus containing Hantaan virus envelope glycoproteins G1 and G2 as an alternative to hantavirus vaccine in mice.

We examined whether a vesicular stomatitis virus (VSV) pseudotype bearing the hantavirus envelope glycoproteins (GPs) G1 and G2 (VSVdeltaG*HTN) could be used as a safe and effective alternative to native hantavirus. Mice were immunized with purified particles of VSVdeltaG*HTN. After the second immunization, all mice produced anti-GP antibody as detected in ELISA and a neutralization test. After the third immunization, the mice were challenged with Hantaan virus. Neither anti-NP antibody production nor Hantaan virus-specific CD8 T-cell reactions were detected in these mice. The present study demonstrated the potential of using a pseudotype VSV system as a tool for developing a hantavirus vaccine.

Animals↗
PubMed2005

Peptide antagonists that inhibit Sin Nombre virus and hantaan virus entry through the beta3-integrin receptor.

Specific therapy is not available for the treatment of hantavirus cardiopulmonary syndrome caused by Sin Nombre virus (SNV). The entry of pathogenic hantaviruses into susceptible human cells is dependent upon expression of the alpha(v)beta(3) integrin, and transfection of human beta(3) integrin is sufficient to confer infectibility onto CHO (Chinese hamster ovary) cells. Furthermore, pretreatment of susceptible cells with anti-beta(3) antibodies such as c7E3 or its Fab fragment ReoPro prevents hantavirus entry. By using repeated selection of a cyclic nonamer peptide phage display library on purified alpha(v)beta(3), we identified 70 peptides that were competitively eluted with ReoPro. Each of these peptides was examined for its ability to reduce the number of foci of SNV strain SN77734 in a fluorescence-based focus reduction assay according to the method of Gavrilovskaya et al. (I. N. Gavrilovskaya, M. Shepley, R. Shaw, M. H. Ginsberg, and E. R. Mackow, Proc. Natl. Acad. Sci. USA 95:7074-7079, 1998). We found that 11 peptides reduced the number of foci to a greater extent than did 80 mug/ml ReoPro when preincubated with Vero E6 cells. In addition, 8 of the 70 peptides had sequence similarity to SNV glycoproteins. We compared all 18 peptide sequences (10 most potent, 7 peptides with sequence similarity to hantavirus glycoproteins, and 1 peptide that was in the group that displayed the greatest potency and had significant sequence similarity) for their abilities to inhibit SNV, Hantaan virus (HTNV), and Prospect Hill virus (PHV) infection. There was a marked trend for the peptides to inhibit SNV and HTNV to a greater extent than they inhibited PHV, a finding that supports the contention that SNV and HTNV use beta(3) integrins and PHV uses a different receptor, beta1 integrin. We then chemically synthesized the four peptides that showed the greatest ability to neutralize SNV. These peptides inhibited viral entry in vitro as free peptides outside of the context of a phage. Some combinations of peptides proved more inhibitory than did individual peptides. In all, we have identified novel peptides that inhibit entry by SNV and HTNV via beta(3) integrins and that can be used as lead compounds for further structural optimization and consequent enhancement of activity.

Amino Acid Sequence↗
PubMed1982

Muroid virus nephropathies and muroid viruses of the Hantaan virus group.

Hemorrhagic fever with renal syndrome (HFRS) came dramatically to the attention of Western medicine in 1951 with the "new" disease becoming a major source of morbidity and mortality in American troops in Korea. Known there as epidemic hemorrhagic fever (EHF) or Korean hemorrhagic fever (KHF), it became apparent that it was the same disease as the endemic (epidemic) hemorrhagic nephroso-nephritis of the Soviet Far East and Songo fever of the Japanese Army in Manchuria. The conjecture that the milder epidemic (endemic) nephropathy of Scandinavia and European Russia was the same or a related disease has now been substantiated with the demonstration of close serological relationship of the Bunyamwera-like virus causing KHF (Hantaan virus) to that of HFRS in Finland, Sweden, European Russia, Greece and Yugoslavia. In the past decade the disease has been recognized as a serious problem in 19 provinces of China and in Japan, where the virus is the Hantaan virus. The severe EHF (or KHF) has its silent reservoir in the wild mouse Apodemus agrarius or in laboratory rats while the less virulent European disease resides in the voles Clethrionomys sp. A mild nonhemorrhagic form of the East Asian nephropathy is carried to man by infected urban rats, Rattus rattus or Rattus norvegicus, in Japan and Korea. All forms are carried to man as a respiratory infection "when a mouse (or rat or vole) coughs". Antibodies to the Hantaan virus have been found in man in India, Iran, Central Africa, Alaska, Bolivia and in wild rodents and urban rats in the USA where human cases of muroid virus nephropathy have not been recognized. Antibody patterns to Hantaan virus and to Scandinavian nephropathia epidemica virus antigens found in human and rodent sera in America and in Sweden, Yugoslavia, and European Russia suggest the possibility of yet a third (or more) virus serotype(s), and also the possible presence of the East Asian type of virus in Europe.

Animals↗
PubMed2005

[Identification of oligopeptides mimicking the virus attachment protein of hantaan virus].

OBJECTIVE: To identify and characterize the epitope associated with the virus attachment protein (VAP) of hantaan virus. METHODS: The monoclonal antibody 3G1 was used as the ligand to biospan from a phage-displayed 12-amino acid peptide library, then the positive phage clones were chosen and sequenced. The amino acid sequences of them were compared with that of hantaan virus G2 in homology. The characteristics of positive phage were studied by IFA and ELISA. A decapeptide combining to cell membrane was observed under laser scanning confocal microscope (LSCM). RESULTS: The conservative motif PX(1-2) HX(0-2) H displaying on positive clones shared homologous amino acid sequence with G2 96YPWHTAKCHY105. CONCLUSION: G2 96YPWHTAKCHY105 might play some roles in virus binding to host cell, and might be a possible key epitope of hantaan virus VAP.

Animals↗
PubMed2000

Clinical evaluation of a vaccinia-vectored Hantaan virus vaccine.

We evaluated a vaccinia-vectored vaccine for hemorrhagic fever with renal syndrome in clinical trials. A Phase I dose-escalation study in 16 volunteers divided into four groups demonstrated that subcutaneous inoculation of approximately 10(7) plaque-forming units of the recombinant virus was safe and immunogenic. Vaccination of a fifth group of 12 volunteers indicated that neutralizing antibody titers to both vaccinia virus and Hantaan virus were enhanced after a second inoculation. Comparing two routes of vaccination showed that scarification effectively induced neutralizing antibodies in vaccinia virus-naive volunteers but that subcutaneous inoculation was superior to scarification in vaccinia virus-immune individuals. A Phase II, double-blinded, placebo-controlled clinical trial was conducted among 142 volunteers. Two subcutaneous vaccinations were administered at 4-week intervals. Neutralizing antibodies to Hantaan virus or to vaccinia virus were detected in 72% or 98% of vaccinia virus-naive volunteers, respectively. In contrast, only 26% of the vaccinia virus-immune volunteers developed neutralizing antibody responses to Hantaan virus. J. Med. Virol. 60:77-85, 2000. Published 2000 Wiley-Liss, Inc.

Antibodies, Viral↗
PubMed1993

Comparison of virulence between Seoul virus strain SR-11 and Hantaan virus strain 76-118 of hantaviruses in newborn mice.

Virulence of hantavirus strain of SR-11 Seoul virus and Hantaan 76-118 (HTN) of Hantaan virus were compared. Infections of both strains were lethal in newborn mice. However, inoculum required to cause lethal infection was about 4,000 times higher for strain HTN (1.65 x 10(3) PFU/mouse/LD50) than for strain SR-11 (0.36 PFU). Thus, both strains were considered pathogenic to newborn mice but they possessed different levels of virulence. The assay system used for these strains in newborn mice proved to be useful in the study of hantavirus virulence. Growth curves of the two strains in CV-7 cell cultures were compared. Strain SR-11 was shown to have higher activity of virus replication and virus release into the culture fluids than strain HTN. The possibility of a relationship between replication activity and high levels of virulence in mice was suggested.

Animals↗
PubMed2004

Cell fusion activities of Hantaan virus envelope glycoproteins.

Hantaan virus (HTNV)-infected Vero E6 cells undergo cell fusion with both infected and uninfected cells under low-pH conditions. Flow cytometry and fluorescence microscopy of HTNV-infected Vero E6 cells showed that envelope glycoproteins (GPs) were located both on the cell surface and in the cytoplasm. Neutralizing monoclonal antibodies (MAbs) against the G1 and G2 envelope GPs inhibited cell fusion, whereas nonneutralizing MAbs against G1 or G2 and MAbs against the nucleocapsid protein (NP) did not. Transfected Vero E6 cells that expressed GPs but not those that expressed NP fused and formed syncytia. These results indicate that HTNV GPs act as fusogens at the cell surface. No fusion activity was observed either in infected Vero cells that were passaged more than 150 times or in BHK-21 cells, although GPs appeared to localize to the cell surface. This variability in fusion induction suggests the involvement of host cell factors in the process of cell membrane fusion.

Animals↗
PubMed1993

High frequency of antibodies to Hantaan virus and hepatitis C virus in chronic haemodialysis patients. Coincidence or cross-reaction?

OBJECTIVES: To address the question of whether there is any coincidence or cross-reaction between hepatitis C virus (HCV) and Hantaan virus (both RNA arboviruses), as well as to assess the frequency of antibodies to the above viruses amongst chronic haemodialysis patients in our region. DESIGN: Collection of serum samples from consecutive unselected chronic haemodialysis patients. SETTING: A tertiary referral center (University Hospital). SUBJECTS: One hundred and fourteen chronic haemodialysis patients were investigated for the presence of antibodies to HCV (anti-HCV) and Hantaan virus disease (anti-HVD). Eleven unselected non-haemodialysis patients with well-defined haemorrhagic fever with renal syndrome (HFRS) were also investigated for the anti-HCV antibodies comprising the disease control group. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The utility of an anti-HVD positive test in chronic haemodialysis patients. RESULTS: Seventeen patients (14.9% 95% confidence interval [CI] 8.4-21.4%) were anti-HCV positive, whereas 15 (13.2%, 95% CI 6.9-19.3%) were anti-HVD positive. An anti-HCV positive test was confirmed by recombinant immunoblot assay (RIBA II) in 88.2%. The presence of anti-HCV antibodies was not associated with transfusions but with the longer duration of haemodialysis (62.8 +/- 29.8 vs. 31.2 +/- 29.3 months, P < 0.001). Anti-HVD antibodies were not associated with transfusions or with the duration of haemodialysis. Three patients were positive for both anti-HCV and anti-HVD antibodies. None of the 11 patients with well-defined HFRS had anti-HCV antibodies. CONCLUSIONS: Chronic haemodialysis patients are a high risk group for HCV infection in association with the duration of haemodialysis and, at least for our geographical area, these patients have to be examined for anti-HVD antibodies especially when a definite causative agent for chronic renal failure is not found. The HVD and HCV infection are not exceptional amongst haemodialysis patients in our region, whereas the possibility of a cross-reaction between these two RNA arboviruses is rather excluded as there was no evidence of HCV infection amongst the patients with well-defined HFRS.

Adolescent↗
PubMed1983

Monoclonal antibodies specific for Hantaan virus.

Six hybridoma cell line producing monoclonal antibodies to Hantaan virus were established by fusion of NS-1 mouse myeloma cells with spleen cells of mice immunized with Hantaan virus strain 76-118. The specificity of these monoclonal antibodies was established by immunoblotting analysis and immunofluorescence. Five of the clones reacted with antigens on the cell surface and in the cytoplasm, and one clone reacted with a determinant expressed only in the cytoplasm of the infected cells. Two of the clones produced antibodies that reacted with a Mr 50,000 polypeptide in virus-infected cellular extracts and purified virus preparations. The monoclonal antibodies were used to examine the antigenic relationship among Hantaan virus strains and between Hantaan virus and Prospect Hill virus and the virus of nephropathia epidemica. Three antibodies were capable of distinguishing between the Lee strain and the 760-118 strain of Hantaan virus and three additional antibodies reacted with determinants shared by both virus strains. None of the six reacted with Prospect Hill virus or the virus of nephropathia epidemica.

Animals↗
PubMed2002

Identification of a cell surface 30 kDa protein as a candidate receptor for Hantaan virus.

Cellular receptors play an important role in virus pathogenesis. As a first step in virus infection, viruses attach to specific receptors on the surface of cells; Hantaan virus infects susceptible cells by attaching to a receptor located on the cell surface. To date, the identity of the Hantaan virus host cell receptor remains unknown. To determine the protein on the cell surface to which Hantaan virus binds, a virus overlay protein-binding assay was performed with radiolabelled virus. A 30 kDa (30K) protein was identified as a putative receptor for Hantaan virus. The specificity of virus interactions with this protein was demonstrated with a competition assay using unlabelled Hantaan virus and poliovirus. Unlabelled Hantaan virus inhibited the binding of radiolabelled Hantaan virus to this 30 kDa protein, whereas poliovirus did not. A polyclonal antibody against the 30K protein blocked binding of Hantaan virus to Vero-E6 cells and, consequently, virus infection. Blocking with the anti-30K antibody reduced virus infection of cells by 70%. These data strongly suggest that the 30 kDa surface protein is a putative receptor for Hantaan virus.

Animals↗