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Biomedical subjects

J W LeDuc

Publications and source records attributed to J W LeDuc.

At least 55 records · Page 3Linked to original sources
PubMed1987

Genomic heterogeneity among human and nonhuman strains of hepatitis A virus.

Cloned cDNA probes derived from the P1 and P2 regions of the genome of HM175 virus, a reference strain of human hepatitis A virus (HAV), failed to hybridize under standard stringency criteria with RNA from PA21 and PA33 viruses, two epizootiologically related HAV strains recovered from naturally infected New World owl monkeys. Hybridization of these probes to PA21 RNA was only evident under reduced stringency conditions. However, cDNA representing the 5' nontranslated region of the HM175 genome hybridized equally to HM175 and PA21 RNA under standard stringency conditions, while a probe derived from the 3' 1,400 bases of the genome yielded a reduced hybridization signal with PA21 RNA. In contrast, no differences could be discerned between HM175 virus and three other HAV strains of human origin (GR8, LV374, and MS1) in any region of the genome, unless increased stringency conditions were used. These results suggest that PA21 and PA33 are unique among HAV isolates and may represent a virus native to the owl monkey. Despite extremely poor homology within the P1 region, which encodes capsid polypeptides, monoclonal antibody analysis confirmed that the immunodominant neutralization epitopes of HAV were highly conserved between HM175 and PA21 viruses. Furthermore, experimental challenge of the owl monkey with successive PA33 and HM175 inocula confirmed a high but incomplete degree of cross-protection. Only one of six monkeys previously infected with PA33 developed recurrent hepatitis 28 days after intravenous HM175 challenge, while none of six monkeys previously infected with HM175 had demonstrable hepatitis following PA33 challenge. These data provide molecular evidence for the existence of HAV strains unique to nonhuman primate species and indicate that strict conservation of antigenic function may accompany substantial genetic divergence in HAV.

Animals↗
PubMed1987

Epidemiology and ecology of the California serogroup viruses.

The California serogroup viruses are important human pathogens, originally discovered in the United States, but now recognized to occur and cause disease in many parts of the world. In addition to their significance to public health, study of their natural history has resulted in a better understanding of the way in which arboviruses are maintained in nature. Viruses of the California serogroup have also been carefully investigated on the molecular level, resulting in a better appreciation of how viruses are constructed, organized, and replicate. William C. Reeves, in whose honor this symposium is held, has contributed throughout his career to each of these fields of endeavor. His pioneering work on these viruses, beginning with the discovery of the prototype California encephalitis virus, has helped to establish the foundations upon which our current understanding of these viruses is built.

Animals↗
PubMed1987

Prospective seroepidemiology of hantaviruses and population dynamics of small mammal communities of Baltimore, Maryland.

We used a prospective seroepidemiological study, in conjunction with a mark-release-recapture protocol, to investigate the transmission of hantaviruses in four rodent species from Baltimore, Maryland, from June 1984 to June 1986. A total of 1,208 captures of 762 rodents provided 984 individual blood samples. The antibody prevalence, as determined by frequency of reciprocal indirect fluorescent antibody (IFA) titers greater than or equal to 32, was 33.9% in rats (Rattus norvegicus, n = 466), 28.3% in meadow voles (Microtus pennsylvanicus, n = 67), 1.4% in house mice (Mus musculus, n = 146), and 1.2% in white-footed mice (Peromyscus leucopus, n = 83). Populations of all rodents were maximal during the fall and winter months, but population trends were not clearly associated with periods of virus transmission. The mean incidence of seroconversion to a Hantavirus for rats was 12.06/100 rats/month, but incidence rates could not be established for other species. Rats which seroconverted were generally sexually mature animals, and there was evidence of transmission throughout the year. Animals which seroconverted to a Hantavirus achieved high IFA titers, and remained seropositive for the duration of the study.

Animals↗
PubMed1987

Epidemiology of Hantaan and related viruses.

Hantaan and related viruses, the causative agents of hemorrhagic fever with renal syndrome (HFRS), are significant human pathogens. Current epidemiologic evidence indicates that these pathogens are disturbed more widely than once believed, and they are likely to cause disease when man comes into close contact with infected rodents. This report summarizes the characteristics of the Hantaanp-related viruses of the genus Hantavirus including epidemiology, ecological characteristics, routes of transmission, and mechanisms of virus maintenance.

Animal Husbandry↗
PubMed1987

Induced oral infection of the owl monkey (Aotus trivirgatus) with hepatitis A virus.

Several species of nonhuman primates have served as animal models for hepatitis A virus (HAV) infection and disease. This study was to determine the suitability of Aotus trivirgatus as an orally induced model for HAV infection and to reconfirm the owl monkey's susceptibility to the intravenous route of inoculation. Animals were inoculated, either orally or intravenously, with varying concentrations of PA-33 strain of HAV. Serum enzymes ALT, AST and GGTP levels were monitored and liver biopsies performed when values exceeded three standard deviations above individualized mean baseline values. All animals had postinoculation elevations of serum ALT and AST values, shed virus in their feces, and were seropositive to HAV by 60 days after inoculation. Eight of the ten postinoculation biopsy specimens had histologic lesions compatible with acute viral hepatitis. We conclude that the owl monkey is a useful and valuable model for the study of HAV disease.

Administration, Oral↗
PubMed1986

Preparation of a prototype inactivated hepatitis A virus vaccine from infected cell cultures.

Studies were conducted on the preparation, inactivation, safety, and immunogenicity of a prototype hepatitis A virus vaccine prepared from infected cell cultures. BS-C-1 cells maintained in medium 199 without serum were infected with the HM175 strain of hepatitis A virus and harvested after 21-28 days. The harvested virus preparation contained 6.8-7.4 (log 10) cell culture infectious doses/ml. After exposure to 1:4,000 formalin at 35 C, the infectivity titer decreased 10(6)-fold in 30 hr at an exponential rate, although virus was detected in 5.0-ml vaccine samples for up to three days. Three separate vaccine lots elicited antibody in all the guinea pigs given three doses. Owl monkeys given three doses of vaccine did not have any evidence of HAV infection but developed antibodies identifiable by radioimmunoassay and serum neutralization tests. After either oral or intravenous challenge with at least 10(6) monkey infectious doses of a virulent field strain of hepatitis A virus, none of the vaccinated monkeys shed virus in their feces or had elevated serum levels of alanine aminotransferase. The findings suggest that an effective inactivated whole virus hepatitis A vaccine can be prepared from cell culture.

Animals↗
PubMed1986

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.

Adolescent↗
PubMed1986

Global survey of antibody to Hantaan-related viruses among peridomestic rodents.

A global serological survey of rodents was conducted to determine the distribution and prevalence of antibody to Hantaan-related viruses, which are the causative agents of haemorrhagic fever with renal syndrome (HFRS) in man. Over 1700 rodent sera from more than 20 sites worldwide were examined by immunofluorescent antibody assay. High-titred positive sera were further tested by plaque reduction neutralization tests with prototype Hantaan virus and urban rat-associated Hantaan-like virus. Antibody-positive rodents were found in most, but not all, sites sampled. The highest antibody prevalence rates were found in Baltimore, MD, USA and Bélem, Brazil, and Rattus norvegicus was the species most often found positive. Bandicota indica and B. bengalensis, species previously not recognized as hosts of hantaviruses, were also positive. Neutralization tests detected antibody in Rattus sera specific for urban rat-associated Hantaan-like virus, but failed to establish the specificity of antibody in Bandicota sera. These results indicate that Hantaan-related viruses exist beyond the currently recognized boundaries of HFRS in man and suggest that human HFRS-like disease might be occurring in other areas of the world where rodent-human contact is common.

Africa↗
PubMed1985

Antigenic and genetic properties of viruses linked to hemorrhagic fever with renal syndrome.

Hemorrhagic fever with renal syndrome (HFRS) comprises a variety of clinically similar diseases of viral etiology that are endemic to and sporadically epidemic throughout the Eurasian continent and Japan. Although HFRS has not been reported in North America, viruses that are antigenically similar to HFRS agents were recently isolated from rodents in the United States. Examination and comparison of eight representative isolates from endemic disease areas and from regions with no known associated HFRS indicate that these viruses represent a new and unique group that constitutes a separate genus in the Bunyaviridae family of animal viruses.

Animals↗
PubMed1985

Isolation of a Hantaan-related virus from Brazilian rats and serologic evidence of its widespread distribution in South America.

A serosurvey of domestic rats was conducted in several South American cities between September 1982 and March 1983 for evidence of hantavirus infection. Antibody-positive rats were found in Belem, São Paulo and Recife-Olinda, Brazil and in Buenos Aires, Argentina, with the highest antibody prevalence rate detected in Belem (30 positive of 54 tested, 56%). A virus isolated from tissues of a Rattus norvegicus captured in Belem, was shown to be antigenically similar to Girard Point viruses isolated from domestic rats captured in the United States and clearly distinct from prototype Hantaan virus, causative agent of Korean hemorrhagic fever in Asia. This represents the first isolation of a virus of the genus Hantavirus from South America and supports previous observations that indicate a widespread distribution of urban rat-associated hantaviruses. The abundance of domestic rats and their regionally high antibody rates suggest that risk of human hantavirus infection in some locations of South America may be significant.

Animals↗
PubMed1985

Serologic evidence of Hantaan-like virus in rodents and man in Thailand.

A serologic survey was conducted to determine the presence of antibody to Hantavirus in rodents in Thailand. Sera from over 300 rodents were tested by an immunofluorescent antibody method. Bandicota indica, a field rodent, was found to have a high incidence of infection (20-24%) in 2 locations. A Hantavirus was isolated from lung samples of B. indica. When sera were tested from humans living in Kanchanaburi and several locations in Bangkok, those people living in close proximity to the infected B. indica had greater than 30% prevalence of positive antibody titers.

Animals↗
PubMed1984

Association of a Sindbis-like virus with Ockelbo disease in Sweden.

An alphavirus isolated from Culiseta mosquitoes has been associated with Ockelbo disease, an exanthema arthralgia syndrome occurring in Sweden. The isolate was made from mosquitoes collected in Edsbyn (central Sweden), an area with considerable Ockelbo disease morbidity. This isolate proved to be indistinguishable from Sindbis virus by complement-fixation and hemagglutination-inhibition tests, and was antigenically related to Sindbis in plaque reduction neutralization tests. Patients with Ockelbo disease developed neutralizing antibodies to the virus in their convalescent sera, suggesting that it is the etiologic agent of the disease.

Aedes↗
PubMed1984

Hantaan-like viruses from domestic rats captured in the United States.

Recent observations that Rattus rodents in Asia harbor Hantaan (HTN)-like viruses associated with hemorrhagic fever with renal syndrome led us to investigate the possibility that similar viruses might be present in the United States. Wharf rats were captured at major port cities, their sera were examined for HTN antibody by immunofluorescent antibody (IFA) assay and tissues from selected antibody-positive rats were examined for HTN antigen. Rats positive for both antibody and antigen to HTN virus were found in Philadelphia, PA and Houston, TX. Infected rats were found clustered in discrete foci where a significant proportion was antibody and antigen positive. Viruses isolated from lung tissues of Rattus norvegicus captured at Philadelphia and Houston were grown in cell culture and shown to be closely related to each other and to the 76-118 strain of HTN virus by IFA, but clearly distinct from HTN by plaque reduction neutralization tests. The isolates appear to be variants of the same new virus, for which the name Girard Point virus is proposed.

Animals↗
PubMed1984

Pathology of hepatitis A infection in the owl monkey (Aotus trivirgatus).

Sequential liver biopsies of owl monkeys that had been experimentally infected with one of two strains of hepatitis A virus (HM-175 or PA-33) were examined for histopathologic alterations. Preinoculation biopsies were normal with only occasional minimal mononuclear cell infiltrates in portal tracts and hepatic lobular parenchyma. Histopathologic features that were present in biopsies taken during the period of elevated serum alanine aminotransferase activity (16-43 days after the intravenous inoculation of virus) included infiltration of predominantly mononuclear inflammatory cells into portal tracts and surrounding parenchyma, degeneration and necrosis of hepatocytes, and hypertrophy of Kupffer cells. Changes were similar in monkeys infected with either HM-175 or PA-33 virus strains. Convalescent biopsies (147-186 days after inoculation) showed resolving lesions with mild portal inflammation and occasional focal collections of inflammatory cells in the parenchyma. These histologic changes are similar to those associated with hepatitis A infection in man, chimpanzees, and several species of marmosets, and support the further use of the owl monkey as a model of human hepatitis A.

Acute Disease↗
PubMed1983

Experimental infection of the New World owl monkey (Aotus trivirgatus) with hepatitis A virus.

Epidemiological studies have demonstrated the susceptibility of the owl monkey (Aotus trivirgatus) to hepatitis A virus, but have not shown an association between infection and histopathological or chemical evidence of liver disease. Therefore, 12 seronegative, colony-bred monkeys were inoculated intravenously with a fecal suspension containing either PA33 strain hepatitis A virus (a strain recovered from a naturally infected Aotus sp.) or HM-175 virus (recovered from a human). Viral antigen was detected by radioimmunoassay in the feces of six monkeys 6 to 17 days after inoculation with PA33 virus, and by 9 to 21 days serum aminotransferase activities were significantly elevated in each. Antibody to the virus developed in each monkey by 28 days after inoculation. Similar findings were noted in five of six monkeys inoculated with HM-175 virus, although the incubation period preceding aminotransferase elevations was somewhat longer (25 to 39 days). Liver biopsies obtained from the 11 infected monkeys demonstrated mild to moderate portal inflammation, as well as random areas of focal necrosis and inflammation extending outward from the portal region. These data confirm the susceptibility of Aotus sp. to hepatitis A virus and indicate that the infection of this primate provides a useful animal model of human hepatitis A.

Animals↗