ABSTRACT
In February 2019, the order Bunyavirales, previously family Bunyaviridae, was amended by new order of 10 families including Hantaviridae family, and now accepted by the International Committee on Taxonomy of Viruses (ICTV). Hantaviridae is now a family of the order Bunyavirales, and the prototype virus species is Hantaan orthohantavirus. The family Hantaviridae is divided into four subfamilies including Mammantavirinae, Repantavirinae, Actantavirinae and Agantavirinae. The subfamily Mammantavirinae is divided into four genera including Orthohantavirus, Loanvirus, Mobatvirus and Thottimvirus. The four Hantavirus species have been found in Korea including three Orthohantaviruses (Hantaan orthohantavirus, Seoul orthohantavirus and Jeju orthohantavirus) and one Thottimvirus (Imjin thottimvirus).
Subject(s)
Humans , Bunyaviridae , Classification , Hantaan virus , Orthohantavirus , Korea , Seoul , VirologyABSTRACT
Hantaviruses belong to the genus Hantavirus and Hantaan, Seoul, Puumala, Belgrade and Sin Nombre viruses are the etiolgic agents of two serious hantaviral diseases of humans. The rodent hosts and the specific etiologic agents of haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) are known and many reported cases occurred in Eurasia and Americas. Wild rodents trapped in 13 different areas of Korea from 1994 to 1998 were investigated against hantavirus infection. A total of 718 wild rodents and 10 species were trapped and found 630 (87.7%) of them were Apodemus agrarius. Indirect immunofluorescent antibody technique (IFAT) was performed for hantaviruses infections using different hantavirus antigens. Hantavirus antibodies were found in 68 (10.8%) out of 630 A. agrarius, 8 (42.1%) of 19 Rattus norvegicus. Among 68 lungs and other tissues of antibody positive A. agrarius, 5 (7.4%) were antigen positive. IFA titers of 5 positive A. agrarius sera showed higher titers against Puumala or Sin Nombre viruses than Hantaan virus. These results suggest that there may be are possibilities of existence of a noble hantavirus in Korean wild rodents.
Subject(s)
Animals , Humans , Rats , Americas , Antibodies , Fever , Hantaan virus , Hantavirus Infections , Hantavirus Pulmonary Syndrome , Orthohantavirus , Hemorrhagic Fever with Renal Syndrome , Korea , Lung , Murinae , Rodentia , Seoul , Sin Nombre virusABSTRACT
Since HantavaxTM, formalin inactivated Hantaan virus vaccine (10,240 ELISA units/ml), has been developed in 1990 to prevent against haemorrhagic fever with renal syndrome (HFRS) caused by Hantaan or Seoul virus, it has been commercially available in Korea. Twenty-one healthy people were booster shot once and twice after primary basic vaccination with HantavaxTM. Seroconversion rates were measured by immunofluorescent antibody technique (IFAT), enzyme-linked immunosorbent assay (ELISA), high density composite particle agglutination (HDPA), and plaque reduction neutralization test (PRNT). Seroconversion rates of 21 vaccinees at one year after primary basic vaccination were 52.3%, 95.2%, 0.0%, 47.6%, and 28.6%, and 13 vaccinees of one month after 1st booster vaccination were 100%, 100%, 30.7%, 100% and 100% by IFAT, ELISA (IgG, IgM), HDPA and PRNT, respectively. Seroconversion rates declined slightly by twenty months, and they were 84.6%, 92.3%, 0.0%, 84.6% and 69.2% by IFAT, ELISA (IgG, IgM), HDPA and PRNT, respectively. Seroconversion rates of 9 vaccinees at three months after 2nd booster vaccination were 100%, 100%, 0.0%, 100%, and 88.9%, and 16 vaccinees at one year after the 2nd booster vaccination were 87.5%, 93.8%, 0.0%, 87.5% and 81.3% by IFAT, ELISA (IgG, IgM), HDPA and PRNT, respectively. Based on the above result HantavaxTM has proved a vigorous anamnestic response after the 1st and the 2nd booster vaccination and has persisted higher fluorescence, agglutination and neutralizing antibody titers in vaccinees.
Subject(s)
Agglutination , Antibodies, Neutralizing , Enzyme-Linked Immunosorbent Assay , Fever , Fluorescence , Formaldehyde , Hantaan virus , Korea , Neutralization Tests , Seoul virus , VaccinationABSTRACT
No Abstract Available.
Subject(s)
Animals , Orthohantavirus , Indonesia , Murinae , ThailandABSTRACT
In Yugoslavia, homorrhagic fever with renal syndrome (HFRS) is one of the important national health problem, but no vaccine has been used to prevent HFRS. Since first HFRS case in 1952, sporadic cases of HFRS occurred every year and over 4,000 registered cases with 1~16% mortality so far. We performed a prospective, randomized double-blind placebo-controlled trial to evaluate the effectiveness of Hantavax(TM) against HFRS in 3,900 healthy adults living in the endemic areas of Yugoslavia. 1,900 people were given 0.5 ml of Hantavax subcutaneously twice at one month interval and a booster shot at one year after. For controls other 2,000 healthy people were given 0.5 ml of physiolosical saline as a placebo. We investigated HFRS cases in both the vaccinated and nonvaccinated groups by monitoring the program for patient registration in the areas from 1996 to 1998, and the effect of vaccine was analyzed epidemiologically No confirmed case of HFRS was observed among 1,900 Hantavax vaccinees, while 20 confirmed cases were observed among 2,000 nonvaccinated control group. There were no remarkable side effects among the vaccinees either locally or in general after inoculation of the vaccine. The Hantavax vaccine showed statistically significant protective efficacy against HFRS among Yugoslavian people.
Subject(s)
Adult , Humans , Fever , Hantaan virus , Orthohantavirus , Hemorrhagic Fever with Renal Syndrome , Mortality , Prospective Studies , YugoslaviaABSTRACT
In Yugoslavia, homorrhagic fever with renal syndrome (HFRS) is one of the important national health problem, but no vaccine has been used to prevent HFRS. Since first HFRS case in 1952, sporadic cases of HFRS occurred every year and over 4,000 registered cases with 1~16% mortality so far. We performed a prospective, randomized double-blind placebo-controlled trial to evaluate the effectiveness of Hantavax(TM) against HFRS in 3,900 healthy adults living in the endemic areas of Yugoslavia. 1,900 people were given 0.5 ml of Hantavax subcutaneously twice at one month interval and a booster shot at one year after. For controls other 2,000 healthy people were given 0.5 ml of physiolosical saline as a placebo. We investigated HFRS cases in both the vaccinated and nonvaccinated groups by monitoring the program for patient registration in the areas from 1996 to 1998, and the effect of vaccine was analyzed epidemiologically No confirmed case of HFRS was observed among 1,900 Hantavax vaccinees, while 20 confirmed cases were observed among 2,000 nonvaccinated control group. There were no remarkable side effects among the vaccinees either locally or in general after inoculation of the vaccine. The Hantavax vaccine showed statistically significant protective efficacy against HFRS among Yugoslavian people.
Subject(s)
Adult , Humans , Fever , Hantaan virus , Orthohantavirus , Hemorrhagic Fever with Renal Syndrome , Mortality , Prospective Studies , YugoslaviaABSTRACT
Hantaan virus (HTNV), the etiologic agent of hemorrhagic fever with renal syndrome (HFRS), belongs to the genus Hantavirus, and has three single negative straded RNA genome segments. HTNV strain Howang isolated from the blood of severe case of Korean HFRS is more virulent than HTNV 76/118 and the M and S genome segments' nucleotide sequence of Howang strain showed 93.5% and 94% homology to each segment of HTNV 76/118. We have obtained 6533 nucleotides long sequence of the L genome segment of Howang strain using reverse transcriptase in conjunction with PCR amplification and compared to other hantaviruses. The messenger sense of the L segment contains one long single long open reading frame of 2151 amino acids, which encodes a deduced RNA dependent RNA polymerase of 246.4 kDa caculated molecular weight protein. The nucleotide sequence of the Lsegment of Howang strain shows 93%, 74%, 66%,65% homology to HTNV 76/118, Seoul virus 80/39, Puumala virus Hallnas B1 and Sin Nombre virus, respectively. The amino acid sequence of the L segment of Howang strain shows 99%, 85%, 68%, 68% homology to HTNV 76/118, Seoul virus 80/39, Puumala virus Hallnas B1 and Sin Nombre virus, respectively.
Subject(s)
Amino Acid Sequence , Amino Acids , Base Sequence , Genome , Hantaan virus , Orthohantavirus , Hemorrhagic Fever with Renal Syndrome , Molecular Weight , Nucleotides , Open Reading Frames , Polymerase Chain Reaction , Puumala virus , RNA , RNA-Dependent RNA Polymerase , RNA-Directed DNA Polymerase , Seoul virus , Sin Nombre virusABSTRACT
In our preliminary study to find antiviral or antitumor agents from Korean natural products, we found that the Shope fibroma virus (SFV) induced fibromas reaching maximum size at 5~6 days with spontaneous disappearance at 15~20 days after SFV intracutaneous inoculation into Korean domestic rabbits. However, the sizes of fibromas of rabbits at day 5 after virus inoculation were significantly different individually. Assuming that the variation of tumor size was due to either susceptibility or the preexisting antibodies against SFV in the Korean domestic rabbits, the rabbits were checked for the antibodies against SFV by IFAT using SFV infected RKl3 cells. The antibody positive rate of normal Korean domestic rabbits was 32.8% and the sizes of the fibromas of the positive rabbits were significantly smaller than those of negative rabbits (p<0.0001). The fibroma sizes were dependent on the antibody titers of rabbits to SFV. The sizes of fibromas after inoculation of SFV into immunized rabbits were about one tenth of those by the first inoculation into normal rabbits. This is the first report on the antibody prevalence against SFV among normal Korean domestic rabbits and it suggest the existence of a wild fibroma virus or related virus in Korea.
Subject(s)
Rabbits , Antibodies , Antineoplastic Agents , Biological Products , Fibroma Virus, Rabbit , Fibroma , Korea , Prevalence , Tumor Virus InfectionsABSTRACT
BACKGROUND: Hantavax(TM) was developed for preven-tion of hemorrhagic fever with renal syndrome caused by Hantaan or Seoul virus in 1990, and has been commer-cially available in Korea since then. Because Hantavax (TM) has such short usage history, the duration of antibody persistency in vaccinees has not been well studied. METHODS: 61 healthy people were immunized subcu-taneously with Hantavax (TM) twice at one month intervals as primary vaccination. 21 vaccinees were tested at 1 ~4 months after primary vaccination and 40 vaccinees were tested at one year after primary vaccination and then one month and 1 ~2 years after booster vaccination. Antibody titers were measured by immunofluorescent assay(IFA), Hantaan virus antigen-coated high density particle agglu-tination assay(HDPA), and plaque reduction neutralization test(PRNT). RESULTS: Seroconversion rates of 21 vaccinees at 1 ~ 4 months after primay vaccination were 20/21(95.2%), 19/21(90.5%) and 14/21(66.7%); seropositivity of 40 vaccinees at one year after primary vaccination was 25/40 (62.5%), 18/40(45.0%), and 9/40(22.5%) by IFA, HDPA, and PRNT, respectively. Seroconversion rates of 8 vaccinees at one month after booster vaccination were 8/ 8(100 %), 8/ 8(100%); antibody persistence rate of 11 vaccinees at 20 months after booster vaccination were 11/ 12 (91.7%), 9/ 12(75.0%), and seroconversion rates of 7 vaccinees at 3 months after second booster vaccination were 7/7(100%) and 6/7(85.7%) by IFA and PRNT, respectively. Geometric mean antibody titers of 21 vaccinees at 1-4 months after primary basic vaccination were 262, 248, 120; and those of 40 vaccinees at one year after primary vaccination were 90, 56, and 24 by IFA, HDPA, and PRNT, respectively. Geometric mean antibody titers of 8 vaccinees at one month after booster vaccination were 852, 183, of 12 vaccinees at 20 months after booster vaccination were 296, 33, and of 7 vaccinees at 3 months after second booster vaccination were 549 and 46 by IFA and PRNT, respectively. CONCLUSION: The booster vaccination is necessary at 12 months after primary vaccination to maintain high levels of antibodies which persist at least two years after booster vaccination.
Subject(s)
Antibodies , Hantaan virus , Hemorrhagic Fever with Renal Syndrome , Korea , Seoul virus , VaccinationABSTRACT
Various hantaviruses were isolated from HFRS patients and various rodent species, in many parts of the world. Bandicotas were captured at Yogyakarta, east region of Sumatura island, Indonesia; and 4 rodents species including Bandicotas were captured at Chiang Rai in Thailand during 1995. Sera were collected from captured andicotas and other rodent spicies were screened for antibody test against Hantaan (HTN), Seoul (SEO), Puumala (PUU) and Sin Hombre (SN) viruses by immunofluoresence antibody assay (IFA). Hantavirus antigen in lung tissues were tested by IFA. Among 55 captured Bandicota indica in Indonesia, 14 (25.5%) were antibody positive against HTN, SEO, PUU and SN virus. Hantavirus antigen were detected from 5 (9.0%) out of 55 lungs tested. Among 34 captured Bandicota indica in Thailand, 9 (26.5%) were antibody positive against HTN, SEO, PUU and SN virus. Among 34 lungs tissues of Bandicota indica examined, 3 (8.8%) were antigen positive. In other rodent species, antibody positive against Hantaviruses of Rattus rattus, Rattus losea and Mus cervicolor were 4/62(6.5%), 5/25(20%), 1/1(100%), respectively. But no one has antigen in their lung tissues. Antigen positive lungs suspension were inoculated into vero E6 cells for virus isolation and 4 viruses were isolated from Indonesian Badicota and 3 viruses from Thailand.
Subject(s)
Animals , Humans , Mice , Rats , Orthohantavirus , Hemorrhagic Fever with Renal Syndrome , Indonesia , Lung , Murinae , Rodentia , Seoul , ThailandABSTRACT
Hantaviruses are members of the family Bunyaviridae, the etiologic agents of Hemorrhagic fever with renal syndrome (HFRS) and Hantavirus Pulmonary Syndrome (HPS). They are negative-sense, single-stranded RNA viruses possessing a large (L), medium (M) and small (S) genomic segment which encodes a viral polymerase, envelope glycoproteins (G1 and G2) and a nucleocapsid (N) protein, respectively. Seoul (SEO) virus, the causative agent of clinically mild HFRS in worldwide, was isolated from lung tissues of urban rat (Rattus norvegicus) captured in Seoul, Korea, 1982. To clarify the antigenic characteristics and the differentiation of serotypes of hantavirus, 8 hybridoma cell lines secreting monoclonal antibodies (MAbs) against SEOV 80-39 strain were produced by fusion of SP2/0-Ag14 mouse myeloma cells with spleen cells of BALB/c mice, immunized with SEOV. Reactivities of these MAbs were examined by the indirect immunofluorescence assay (IFA), enzyme linked immunosorbent assay (ELISA), immunoblot, high density particle agglutination (HDPA) and plaque reduction neutralization test (PRNT). Eight out of 235 hybridomas secreted MAbs of Seoul virus 80-39 continuously, and these eight MAbs were all IgG. The isotypes of these 8 MAbs are; one clone (F3-3C) was IgG1, six (F1-1B9B, F1-3B, F1-3D, F4-1E, F4-3F, F4- 6C) were IgG2a and one (F1-1B9F) was IgG2b. Seven MAbs (F1-1B9B, F1-1B9F, F1-3B, F1- 3D, F3-3C, F4-1E, F4-3F) reacted with nucleocapsid protein (M.W. 50K) of SEOV by immunoblot. All eight MAbs were cross-reacted with Hantaan (HTN) virus, one (F4-3F) was cross-reacted with Puumala (PUU) virus and two (F1-1B9B, F1-3B) were cross-reacted with Prospect Hill (PH) virus by IFAT. None of these 8 MAbs had neutralizing activity.
Subject(s)
Animals , Humans , Mice , Rats , Agglutination , Antibodies, Monoclonal , Bunyaviridae , Cell Line , Clone Cells , Enzyme-Linked Immunosorbent Assay , Fluorescent Antibody Technique, Indirect , Glycoproteins , Orthohantavirus , Hantavirus Pulmonary Syndrome , Hemorrhagic Fever with Renal Syndrome , Hybridomas , Immunoglobulin G , Korea , Lung , Neutralization Tests , Nucleocapsid , Nucleocapsid Proteins , RNA Viruses , Seoul virus , Seoul , SpleenABSTRACT
A large number of viruses belonging to Genus Hantavirus in Family Bunyaviridae are etiologic agents for hemorrhagic fever with renal syndrome (HFRS), or hantavirus pulmonary syndrome (HPS). Hantaan (HTN), Seoul (SEO), Belgrade (BEL), Puumala (PUU) serotype viruses are well known causative agents for HFRS in Eurasian continent. Among those viruses Hantaan and Seoul serotypes are well known to cause HFRS in Korea, but there are some sporadic incidence by other than Hantaan or Seoul viruses. Recently we have developed the combined Hantaan-Puumala virus vaccine to prevent world-wide occurring HFRS. This combined vaccine is formalin inactivated, suckling mouse and suckling hamster brain extracts for Hantaan and Puumala viruses, respectively. Protein contents of this purified candidate vaccine is 27 microgram/ml, which contains 1,024 ELISA antigen units to each virus, but content of myelin basic protein which is causing experimental allergic encephalomyelitis is legs than 0.1 ng/ml. Thirty hamsters were given twice at one month interval intra-muscularly and bled on 30 days after each vaccination from retro-orbital sinus vein. Antibody titers were tested against 5 major serotype viruses, Hantaan, Seoul, Belgrade, Puumala and Sin Nombre viruses by IFA and PRNT. The mean IF antibody titers on 30 days after primary shot were 78.4, 68.8, 68.8, 37.9, and 15.6; mean neutralizing antibody titers were 65.4, 12, 6.1, 65.6 and 0.5 against Hantaan, Seoul, Belgrade, Puumala and Sin Nombre viruses, respectively. The mean IF antibody titers on 30 days after booster shot were 686.9, 567.5, 550.4, 516.3, and 430.9; and neutralizing antibody titers were 710.8, 41.9, 24.3, 409.9, and 1.6 against Hantaan, Seoul, Belgrade, Puumala and Sin Nombre viruses, respectively.
Subject(s)
Animals , Cricetinae , Humans , Mice , Antibodies, Neutralizing , Brain , Bunyaviridae , Encephalomyelitis, Autoimmune, Experimental , Enzyme-Linked Immunosorbent Assay , Formaldehyde , Orthohantavirus , Hantavirus Pulmonary Syndrome , Hemorrhagic Fever with Renal Syndrome , Incidence , Korea , Leg , Myelin Basic Protein , Puumala virus , Seoul , Seoul virus , Sin Nombre virus , Vaccination , VeinsABSTRACT
We developed a sensitive, nested reverse transcription-polymerase chain reaction (RT-PCR) to detect Hantaan, Seoul, Belgrade, Puumala and Sin Nombre viruses in animal tissues. Total RNA was extracted from blood, lung or kidney samples of experimentally-infected hamsters by using the guanidine isothiocyanate buffer-acid phenol-chloroform method. Genus-reactive outer primers were derived from the consensus region of the G1 gene sequences of several hantaviruses. Serotype-specific primers were selected within the region amplified by the outer primers. To examine the sensitivity and specificity of the test, we diluted known quantities of Hantaan, Seoul, Belgrade, Puumala and Sin Nombre viruses in human or hamster immune sera before performing the nested RT-PCR. We could detect as little as 1 pfu of virus, even in the presence of high-titer neutralizing antibodies, and the serotype-specific primers amplified only homologous serotype viruses. RT-PCR with these primers demonstrated virus in the blood of experimentally-infected hamsters as early as four days to as late as 30 days after infection.4 comparison of a standard immunofluorescent antibody screening test (IFAT) to nested RT-PCR with RNA extracted from lung or kidney tissues of the hamsters, demonstrated that RT-PCR to be more sensitive for identifying viruses in these tissues.
Subject(s)
Animals , Cricetinae , Humans , Antibodies, Neutralizing , Consensus , Discrimination, Psychological , Guanidine , Orthohantavirus , Immune Sera , Kidney , Lung , Mass Screening , RNA , Sensitivity and Specificity , Seoul , Sin Nombre virusABSTRACT
Hantaan virus Howang strain which isolated from the blood of severe case of Korean hemorrhagic fever is more virulent than HTN 76/118 and showed different RFLP from partial PCR amplified M genome segment to established Hantaan serotype viruses. We have determined the nucleotide sequence of the M and S genome segments and compared to HTN 76/118. The M and S segment of Howang strain has 3615 and 1696 nucleotides long, respectively. The M segment sequence of Howang strain is one mucleotide shorter than HTN 76/118. The sequence data of Howang strain shows 93.5% homology to HTN 76/118. One long open reading frame, which stoats from 41nt. to 3448nt. of the M segment and from 37nt. to 1326nt. of the S segment, exist to on complementary sense of the virus genome. There are no significant difference between HTN 76/118 and Howang strain on hydrophobicity of deduced polypeptides, but has slight difference on secondary structure.
Subject(s)
Base Sequence , Genome , Hantaan virus , Hemorrhagic Fever with Renal Syndrome , Hydrophobic and Hydrophilic Interactions , Nucleotides , Open Reading Frames , Peptides , Polymerase Chain Reaction , Polymorphism, Restriction Fragment LengthABSTRACT
The purpose of this study is to delineate the histopathologic findings of the spleen after Hantaan viral inoculation, which is the largest lymphoid organ in rats, and to identify the viral location by anti-Hantaan virus (HTNV) monoclonal antibody. All the sixty one suckling rats of less than twenty four hours of age were used. Except twenty one rats of control group, twenty-five rats inoculated intracerebrally for the early change and fifteen suckling rats inoculated intramuscularly for the late change were uniformly susceptible to lethal infection with the ROK 84-105-1 strain of seed HTNV. The characteristic histopathologic findings were; appearance of macrophages below the splenic capsule on the 3rd day, small lymphocytes around the periarteriolar sheath on the 5th day increasing in numbers on the 7th day, and a markedly expanded marginal zone with some immunoblasts and plasma cells as well as decreased extramedullary hematopoiesis on the 9th and 14th days. Time of onset of histopathologic changes in spleen thickness, appearance of medium and large lymphocytes and degree of extramedullary hematopoiesis were influenced by inoculation route, whereas expansion of the marginal zone was affected by postnatal age.