Seoul Virus Research Articles

Seroprevalence of antibodies to hantaviruses and leptospires in selected Italian population groups.

A study of hantaviral and leptospiral antibodies in selected population groups was performed. Among high risk subjects in the Rome area, Hantaan antibody was found in mammalogists (10%) and dialysis patients (6%), while none of the trappers, oarsmen, river policemen and firemen studied tested positive for antibodies to hantaviruses. In occupationally-exposed subjects (farmers, rangers, lumbermen, hunters) from rural and densely forested areas of northern Italian regions, the prevalence of Hantaan antibody ranged from 3.3% to 8.8%. In the positive cases the comparative antibody titration using different hantaviruses showed a predominance of Hantaan virus (titer 1:128) compared to Puumala virus (titer 1:32); no reactivity was observed with Seoul or Prospect Hill viruses. In Rome, leptospiral antibodies were found in trappers (21%) and oarsmen (5%) at a titer of 1:50 or more, with a predominance for the L. icterohaemorrhagiae serotype (85%). In the Alpine areas the leptospiral antibody prevalence was 12% and L. icterohaemorrhagiae and L. bratislava were the predominant serotypes. The presence of hantavirus infections, suspected after the first epidemiological survey conducted in central Italy, is now supported by the new data obtained in northern Italian regions. Furthermore, the recent observation of one case of Hemorrhagic Fever with Renal Syndrome (HFRS) in the Udine area, not far from the Yugoslavian border, strongly confirms the presence of one or more hantaviruses in Italy.

Human-rodent contact and infection with lymphocytic choriomeningitis and Seoul viruses in an inner-city population.

We collected 1180 sera and 1363 questionnaires with information on demography, rodent exposure, and history of travel from persons visiting a sexually transmitted disease (STD) clinic in Baltimore between 1986-1988. Serological tests for two rodent-borne viruses detected antibodies to lymphocytic choriomeningitis virus (LCMV) in 54 individuals (4.7%; n = 1149) and antibodies to Seoul virus (SEOV) in three persons (0.25%; n = 1180). Antibody prevalence to LCMV increased with age, but there were no racial or sexual differences. Neutralization tests and questionnaire responses implicated a domestic, rat-borne hantavirus as the source of SEOV antibody. Self-reported human-rodent contact indicated more exposure to house mice than rats within residences, although rats were more commonly sighted on streets. Infections with rodent-borne viruses were rare compared to the high rates of reported contact.

A Retrospective Analysis of Sera Collected by the Hemorrhagic Fever Commission during the Korean Conflict

More than 600 sera from 245 patients with a clinical diagnosis of hemorrhagic fever were preserved by the Hemorrhagic Fever Commission during the Korean Conflict, 1951-1954. These sera were tested for IgM- and IgG-specific antibodies to Hantaan virus by enzyme immunoassay and for hantaviral antigen by immunoassay; one serum from each patient was tested by plaque reduction neutralization using both Hantaan and Seoul viruses. Only 15 patients failed to develop antihantaviral antibodies; most sera contained high titered IgM antibody on admission, and all were IgM-seropositive by day 7 after onset. Attempts to detect hantaviral antigen were unsuccessful. All seropositive patients had highest plaque reduction neutralization titers to Hantaan virus, suggesting that this virus was responsible for the disease seen. These results confirm that hemorrhagic fever of the Korean Conflict was due to Hantaan virus and demonstrate that measurement of specific IgM antibody is the method of choice for diagnosis of acute disease.

Hantavirus strains isolated from rodentia and insectivora in rural China differentiated by polymerase chain reaction assay

Polymerase chain reaction (PCR) assay and other techniques were applied to differentiate Hantavirus strains isolated from different animal hosts and geographic regions in China. Two groups of related strains, Hantaan and Seoul, have been classified by cross-neutralization, radioimmunoprecipitation (RIP), and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) assays. The molecular weights of glycoprotein 1 (G1) of Hantaan and Seoul viruses were 72k and 80k, whereas those of the nucleocapsid (N) and glycoprotein 2 (G2) remained the same, respectively. The PCR assay was used to differentiate these isolates using synthetic oligonucleotide primers selected from various regions of the M genome of 76118 and R22 strains. 76118-specific primers amplified only the RNAs extracted from Hantaan strains while R22-specific primers, the RNAs from Seoul strains. The PCR results for classification are consistent with those obtained by cross-neutralization, RIP and SDS-PAGE assays.

Hantavirus-related Acute Interstitial Nephritis in Western Europe. Expansion of a World-wide Zoonosis

We report the clinical, biological and serological characteristics of 76 cases of Hantavirus-induced acute interstitial nephritis diagnosed in Belgium and France between 1977 and 1986. The disease is characterized by a fever of sudden onset promptly accompanied by pain in the loin or abdomen, nausea and vomiting, myalgias and occasionally with acute myopia and conjunctival injection. Within a week acute renal failure develops, necessitating haemo- or peritoneal dialysis in up to 10 per cent of patients. Transient proteinuria, microscopic haematuria and leukocyturia are observed simultaneously. Thrombocytopenia and mild elevations of hepatic enzymes, LDH and CPK, as well as biological signs of acute inflammatory reaction are observed, lasting for a few days. Spontaneous complete recovery is the rule. This picture is virtually identical with that of nephropathia epidemica, a Hantavirus nephropathy observed in northern Europe. This conclusion is supported by the observation of elevated antibody titres against the Puumala virus, the agent of nephropathia epidemica. This rodent-borne infection is markedly milder than that caused by other Hantaviruses such as the Hantaan or the Seoul virus in Asia. Acute interstitial disease due to Hantavirus should be included in the differential diagnosis of febrile acute renal failure.

EFFECTS OF HANTAVIRAL INFECTION ON SURVIVAL, GROWTH AND FERTILITY IN WILD RAT (RATTUS NORVEGICUS) POPULATIONS OF BALTIMORE, MARYLAND

Survival, growth rates, body size and fertility of wild caught Norway rats (Rattus norvegicus), infected and uninfected with a Hantavirus (antigenically related to Seoul virus), were compared. No differences were found in the survival of seronegative versus seropositive rats, as measured by mark-recapture experiments. Growth rates, as measured by weight gain but not by increased body length, were slower in seropositive, sexually mature (greater than 200 g) rats, although no differences in the ultimate body size of infected versus uninfected rats were found. No differences in external measures of sexual maturity, or in embryo counts or testes sizes, were found for infected versus uninfected rats. We conclude that hantaviral infections have little or no impact on demographic processes in Norway rat populations.

Serologic Evidence of Hantaviral Infections within Small Mammal Communities of Baltimore, Maryland: Spatial and Temporal Patterns and Host Range

Serologic evidence was used to investigate the spatial and temporal distribution and host range of hantaviruses in small mammal communities in Baltimore, MD. Immunofluorescent antibody (IFA) reactive to a Baltimore rat isolate of Seoul virus was detected in 44% of 404 Norway rats captured at 4 park or residential locations; 21% of 121 meadow voles captured at 4 park locations possessed significant IFA titers to Prospect Hill virus. Evidence from plaque neutralization assay of rodent sera suggested that Seoul virus and Prospect Hill virus circulated concurrently in voles and rats, respectively, at 1 park. No cross infection of virus between these primary reservoir species was observed, as determined by higher specific neutralizing antibody titers to the characteristic virus for each host species. Only 4% of 449 house mice and 1% of 94 white-footed mice captured at the same sites as the primary host species were seropositive to hantaviruses, despite extensive demonstrated overlap in time and space with the primary host species.

A clinical study of hemorrhagic fever with renal syndrome caused by Seoul virus infection.

The clinical findings of 29 patients with hemorrhagic fever with renal syndrome (HFRS) caused by Seoul virus were evaluated and compared with the previously reported clinical findings of classic Korean hemorrhagic fever (KHF).The diagnoses of these patients were made by hemagglutination inhibition test.The results were as follows: The disease occurred predominantly in males with a high incidence in the third and fourth decades of life.The highest incidence of the disease occurred in October–December.Major symptoms were fever, abdominal or flank pain, vomiting and myalgia.Major signs were petechia, CVA tenderness, pharynegeal injection, and conjunctival infection, but these signs were much less common than in patients with classic KHF.The treatments were mainly conservative and there was no fatal case in the study subjects.These findings suggest that the clinical course of Seoul virus infection may be much milder than that of classic KHF and the outcome may be more favorable.

Characterization of Hantaan Virus Envelope Glycoprotein Antigenic Determinants Defined by Monoclonal Antibodies

A panel of 24 monoclonal antibodies (MAbs) to the G1 or G2 envelope glycoproteins of Hantaan virus were used to determine the surface topography and functional properties of antigenic sites. Nine distinct, partially overlapping antigenic sites, two on G1 and seven on G2, were demonstrated by competitive binding assays. Analyses of the antigenic sites by haemagglutination (HA) inhibition and plaque-reduction neutralization tests showed that all of the sites, except one on G1, were related to viral HA. Only one of the G1 antigenic sites and two of the G2 sites were involved in virus neutralization. These results suggest that certain epitopes related to HA were not critical for virus neutralization. The nine antigenic sites could be further divided into 13 based upon the serological cross-reactivity of MAbs with viruses representative of each of the four known antigenic groups within the Hantavirus genus of Bunyaviridae, i.e. Hantaan, Seoul, Puumala and Prospect Hill viruses.

Leakey virus: a new hantavirus isolated from Mus musculus in the United States.

A hantavirus, designated Leakey virus, was isolated from a Mus musculus captured in Real County, Texas, U.S.A. in August 1986. Virus-specific fluorescence was first detected 13 days after inoculation of Vero-E6 cells with spleen tissue from the seropositive M. musculus. Ultrastructurally, the new isolate resembled other hantaviruses. Leakey virus induced a fatal meningoencephalitis in infant Fischer rats, with viral antigen detectable in brain, lung, liver, kidney and spleen. Serum dilution, plaque reduction neutralization tests indicated that Leakey virus was antigenically distinct from Hantaan, Seoul, Puumala and Prospect Hill viruses, and therefore constitutes a new serotype.

Cell-mediated immunity to virus causing haemorrhagic fever with renal syndrome: generation of cytotoxic T lymphocytes.

Cytotoxic T lymphocytes (CTLs) were generated when spleen cells from mice infected with viruses causing haemorrhagic fever with renal syndrome were stimulated in vitro with syngeneic cells infected with viruses. These cytotoxic effector cells, with Lyt2+ L3T4- markers on their surface, demonstrated H-2 restriction. CTLs induced by Hantaan virus (76-118 strain) or Seoul virus (B-1 strain) showed cross-reactivity with infected target cells. Hantaan virus infection induced a higher CTLs response than Seoul virus infection, although the antibody responses to these two viruses and the replication of the two virus strains in athymic nude mice were not significantly different. Viral antigen detected with a monoclonal antibody reacting with nucleocapsid antigen was observed mainly in the cytoplasm of macrophages infected with Hantaan virus, but in the nucleus of cells infected with Seoul virus. The major viral antigens recognized by CTLs are discussed on the basis of these findings.

Aerosol transmission of Hantaan and related viruses to laboratory rats.

Hantaan, Seoul, and Puumala viruses were transmitted to 12-16-week-old female Wistar Rattus norvegicus by inhalation. The rodent infectious dose for each virus by intramuscular inoculation and by inhalation was determined, as was the infectious dose for Vero E-6 cells by direct plaque assay.

Clinical and epidemiological aspects of hemorrhagic fever with renal syndrome (HFRS) in Greece.

Twenty-three cases of hemorrhagic fever with renal syndrome were serologically diagnosed in rural populations of Greece between 1982 and 1985. The clinical picture of the disease was severe, (3 deaths recorded among 23 cases) and more closely resembled Korean hemorrhagic fever than nephropathia epidemica. Examination of patients' sera by indirect immunofluorescence (IFA) assays and plaque reduction neutralization (PRNT) tests using Hantaan 76-118, Puumala, and Seoul (Urban rat-associated Hantaan-like) viruses, suggested that the virus existing in Greece is either prototype Hantaan virus or a distinct virus which is closely related to Hantaan. Small mammal survey results suggest that Apodemus flavicollis may be the host of this virus. Serosurvey results of 2,653 blood samples taken from apparently healthy residents (farmers, shepherds, and woodcutters) from 22 of 54 counties in Greece, showed the percentage of seropositives to be 4%, with a range from 0 to 14%. Fifteen of 22 counties were characterized as endemic areas of the virus due to the presence of seropositive individuals. In 6 of the 15 endemic areas, overt human disease was serologically diagnosed.

Epidemiological investigations following an outbreak of hemorrhagic fever with renal syndrome in Greece.

Epidemiological investigations were conducted following an outbreak of hemorrhagic fever with renal syndrome (HFRS) which occurred in the state of Epirus, northwestern Greece, in July and August 1983. A total of 8 patients were hospitalized during the outbreak; 3 were severely ill and 1 died. A serosurvey made in May 1984 sampled 184 of the approximately 400 residents of the village of Tsepelovo, where 4 patients resided, and found 12 (6.5%) persons, including convalescent sera from 4 patients, with antihantaviral antibody by immunofluorescent antibody (IFA) tests. Small mammal collections found house rats common in the village, but none exhibited anti-hantaviral antibody. Collections in nearby fields and mountains found Apodemus flavicollis rodents common, and 2 (6%) of 33 captured had high IFA anti-hantavirus antibody. Virus isolation attempts from rodent tissues were unsuccessful. Testing of convalescent patients' sera by IFA and plaque reduction neutralization tests indicated that the etiological agent was neither Puumala virus nor Seoul virus, but appears to be a strain of Hantaan virus or perhaps a new virus. The rodent host of this virus may be A. flavicollis, and the distribution of this species corresponds with previously reported cases of severe HFRS described elsewhere in central Europe.