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Biomedical subjects

Charles F Fulhorst

Publications and source records attributed to Charles F Fulhorst.

13 recordsLinked to original sources

Characterization of shock in a hamster model of hantavirus infection.

Human hantavirus cardiopulmonary syndrome (HCPS) due to Andes, sin nombre and other hantaviruses is characterized by severe pulmonary capillary leak and cardiogenic shock. Hamsters, the only animal manifesting HCPS-like disease, were instrumented with radiotelemeters that enabled ambulatory intracarotid blood pressure recording within an animal biosafety level-4 facility. Following infection with Andes virus, blood pressure and heart rate decreased slowly in a biphasic manner during the first 7 days of infection, followed by a rapid fall in pressure and rapid increase in heart rate during the 10-20 h preceding death on day 9 or 10. The preterminal narrowing of pulse pressure was consistent with a cardiogenic impairment. Heart rate variability analysis implicated increased sympathetic nervous system activity as seen in human HCPS. The hamster model of HCPS mimics not only the pulmonary capillary leak but also the hypotension characteristic of human HCPS.

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Catacamas virus, a hantaviral species naturally associated with Oryzomys couesi (Coues' oryzomys) in Honduras.

The primary objective of this study was to extend our knowledge of the geographical distribution, genetic diversity, and natural host associations of the hantaviruses indigenous to North America. Antibody to a hantavirus was found in 5 (20.8%) of 24 Coues' oryzomys (Oryzomys couesi) and none of 41 other rodents captured near the town of Catacamas in eastern Honduras, and a hantavirus was isolated from one of the antibody-positive Coues' oryzomys. Analyses of nucleotide and amino acid sequence data indicated that the viral isolate is a strain of a novel hantaviral species (proposed species name "Catacamas virus") that is phylogenetically most closely related to Bayou virus, a hantaviral species that is principally associated with Oryzomys palustris (marsh oryzomys) in the southeastern United States. Catacamas virus is the first evidence for the occurrence of a hantaviral species in Honduras and the first evidence that a hantaviral species is naturally associated with an Oryzomys species other than O. palustris.

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Maporal virus, a hantavirus associated with the fulvous pygmy rice rat (Oligoryzomys fulvescens) in western Venezuela.

Oryzomine rodents in the southeastern United States, Panama, and southern South America are natural hosts of 6 of the 13 viruses known to cause hantavirus pulmonary syndrome. The purpose of this study was to extend our knowledge of the geographical distribution and genetic diversity of the hantaviruses associated with oryzomine rodents in South America. An infectious hantavirus was isolated from two fulvous pygmy rice rats captured in western Venezuela. Analyses of complete nucleocapsid protein and glycoprotein precursor sequences indicated that the isolates are strains of a novel hantavirus (proposed name "Maporal") which is phylogenetically most closely related to the viruses known to cause hantavirus pulmonary syndrome in southern South America.

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Phylogeny of the Venezuelan arenaviruses.

Guanarito virus (the etiologic agent of Venezuelan hemorrhagic fever, VHF) and Pirital virus coexist in the region of Venezuela in which Venezuelan hemorrhagic fever is endemic. The purpose of this study was to extend our knowledge of the evolutionary relationship between these two arenaviruses. We determined that the large genomic segments of Guanarito virus and Pirital virus are similar in size and identical in structural organization to the large genomic segments of other South American arenaviruses. For example, the Z proteins and RNA-dependent RNA polymerases of Guanarito virus and Pirital virus are encoded in nonoverlapping open reading frames of opposite polarities. Phylogenetic analyses of Z protein gene nucleotide sequences and RNA-dependent RNA polymerase gene nucleotide sequences grouped Pirital virus with Pichindé virus (a South American arenavirus which, like Pirital virus, does not appear to be pathogenic for humans) and placed the Pirital-Pichindé lineage in a sister relationship to a lineage represented by Guanarito virus and the three other arenaviruses known to cause hemorrhagic fever in South America. These results are concordant with the results of studies on the phylogeny of the arenavirus small genomic segment. Thus, the exchange of genomic elements between Guanarito virus and Pirital virus via recombination or reassortment likely did not contribute to the emergence of Venezuelan hemorrhagic fever.

Amino Acid Sequence↗

Epizootiology of arenaviral infections in the white-throated woodrat (Muridae: Sigmodontinae) and other woodrats in Arizona.

The purpose of this study was to extend and refine our knowledge of the geographical distribution and natural host relationships of the arenaviruses associated with woodrats indigenous to Arizona. Antibody to a Tacaribe serocomplex virus was found in 112 of 1,250 white-throated woodrats, five of 208 Mexican woodrats, one of 114 Stephen's woodrats, and none of 862 other rodents captured at 51 sites in 10 counties in Arizona. Of the 112 antibody-positive white-throated woodrats, 109 (97.3%) were captured within extensive, dense patches of prickly pear cactus and cane cholla in three counties in mid-central Arizona. Analysis of the serological and zoographical data suggested that white-throated woodrats usually become infected early in life and that the distribution of antibody-positive white-throated woodrats in Arizona is not linked to a specific biome.

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Maporal viral infection in the Syrian golden hamster: a model of hantavirus pulmonary syndrome.

Hantavirus pulmonary syndrome (HPS) is a severe and often fatal rodent-borne zoonosis. Maporal (MAP) virus is a newly discovered hantavirus that originally was isolated from an arboreal rice rat captured in central Venezuela. The results of this study indicate that MAP virus in the Syrian golden hamster (Mesocricetus auratus) can cause a disease that is clinically and pathologically remarkably similar to HPS. The similarities include the time course of clinical disease, presence of virus-specific IgG at the onset of clinical disease, subacute pneumonitis, rapid onset of diffuse alveolar edema in the absence of necrosis, hepatic-portal triaditis, mononuclear-cellular infiltrate in lung and liver, widespread distribution of hantaviral antigen in endothelial cells of the microvasculature of lung and other tissues, and variable lethality. These similarities suggest that the MAP virus-hamster system is a useful model for studies of the pathogenesis of HPS and for the evaluation of potential therapeutic agents.

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Phylogeny of New World arenaviruses based on the complete coding sequences of the small genomic segment identified an evolutionary lineage produced by intrasegmental recombination.

Previous studies suggested that the small genomic segments (S-RNA) of the South American arenaviruses (SA-AVs) represent three phylogenetic lineages (designated A, B, and C) and indicated that the S-RNA of Whitewater Arroyo virus (WWAV) (a North American arenavirus [NA-AV]) is a product of genetic recombination between a lineage A and lineage B virus. The purpose of this study was to extend our knowledge on the phylogenetic relationships between WWAV, the two other NA-AVs (Tamiami and bear canyon), and the 15 SA-AVs. Therefore, we determined the complete sequence of the S-RNA of nine arenaviruses previously uncharacterized or sequenced only partially. Phylogenetic analyses of the two complete coding regions indicated that the S-RNA of the three NA-AVs have descended from a single ancestral virus, which was the product of recombination between a lineage A and lineage B arenavirus. No such evidence for genetic recombination was found in cupixi virus (a novel arenavirus isolated from a wild rodent captured in Northeastern Brazil) or the 14 other SA-AVs. The recombinant nature of the S-RNA of NA-AVs distinguishes them from the SA-AVs, and thus, indicates that the NA-AVs represent a fourth phylogenetic lineage in the Tacaribe serocomplex.

Amino Acid Sequence↗

Exposure to rodents and rodent-borne viruses among persons with elevated occupational risk.

Persons who have frequent contact with rodents as part of their occupation may be at increased risk of exposure to rodent-borne viruses such as Sin Nombre virus (SNV), the agent of hantavirus pulmonary syndrome, and Whitewater Arroyo virus (WWA), a New World arenavirus. Eighty-one persons with possible occupational exposure to rodents completed questionnaires and provided specimens for serologic testing. Seventy-two participants reported handling rodents as part of their job. The mean total number of rodents handled during participants' careers was approximately 2200. IgG antibody to lymphocytic choriomeningitis virus was detected in serum from one (1.2%) participant. IgG antibody to SNV, WWA, and Amapari viruses was not detected in any of the serum specimens. Despite considerable exposure to rodents, participants did not have significant serological evidence of exposure to rodent-borne viruses.

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Bear Canyon virus: an arenavirus naturally associated with the California mouse (Peromyscus californicus).

Thirty-four rodents captured in southern California were studied to increase our knowledge of the arenaviruses indigenous to the western United States. An infectious arenavirus was isolated from 5 of 27 California mice but none of the 7 other rodents. Analyses of viral nucleocapsid protein gene sequence data indicated that the isolates from the California mice are strains of a novel Tacaribe serocomplex virus (proposed name "Bear Canyon") that is phylogenetically most closely related to Whitewater Arroyo and Tamiami viruses, the only other Tacaribe serocomplex viruses known to occur in North America. The discovery of Bear Canyon virus is the first unequivocal evidence that the virus family Arenaviridae is naturally associated with the rodent genus Peromyscus and that a Tacaribe serocomplex virus occurs in California.

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Experimental infection of the Sigmodon alstoni cotton rat with Caño Delgadito virus, a South American hantavirus.

Forty-eight Sigmodon alstoni (Alston's cotton rat) were inoculated with Caño Delgadito (CDG) virus to extend our knowledge and understanding of the natural host relationships of the hantaviruses indigenous to the Americas. Infectious CDG virus was recovered from oropharyngeal secretions, urine, or solid tissues of nine of 12 animals killed on day 9 post-inoculation (PI), 14 of 24 animals killed on day 18 or 27 PI, and none of 12 animals killed on day 54 PI. In addition, virus-specific RNA was detected in the kidneys of six of the 12 animals killed on day 54 PI, and adult cotton rats inoculated with the kidneys of four animals killed on day 54 PI developed antibody to CDG virus. Collectively, the results indicate that CDG virus can establish lengthy (perhaps lifelong) infections in Alston's cotton rat and thus support the concept that S. alstoni is the principal host of CDG virus.

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Natural host relationships and genetic diversity of Whitewater Arroyo virus in southern Texas.

The purpose of this study was to refine our knowledge of the natural host relationships of Whitewater Arroyo (WWA) virus. Two hundred eight rodents, representing nine species, were captured in July 1999 on the Chaparral Wildlife Management Area in southern Texas and tested for evidence of arenavirus infection. Antibody to an arenavirus was found in seven (21.9%) of 32 southern plains woodrats (Neotoma micropus) and none of 168 other rodents. Infectious WWA virus was isolated from four antibody-positive southern plains woodrats, one of 25 antibody-negative southern plains woodrats, and none of 176 other rodents. Collectively, the results indicate that the southern plains woodrat is a principal host of WWA virus in southern Texas. Analyses of viral gene sequence data revealed substantial genetic diversity among WWA virus strains isolated from the woodrats, suggesting that multiple variants of the virus can coexist in a single woodrat species in a small geographic area.

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