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F A Murphy

Publications and source records attributed to F A Murphy.

33 records · Page 2Linked to original sources
PubMed1976

Segmented genome and nucleocapsid of La Crosse virus.

La Crosse (LAC) virions purified by velocity and equilibrium gradient centrifugation contained three single-stranded RNA species. The three segments had sedimentation coefficients of 31S, 25S, and 12S by sodium dodecyl sulfate-sucrose gradient centrifugation. By comparison with other viral and cellular RNA species, the LAC viral RNAs had molecular weights of 2.9 x 10(6), 1.8 x 10(6), and 0.4 x 10(6). Phenol-sodium dodecyl sulfate-extracted LAC virion RNA was not infectious for BHK-21 cell cultures under conditions in which Sindbis viral RNA was infectious. Treatment of LAC virus with the nonionic detergent Triton X-100 and salt released three nucleocapsid structures, each containing one species of virion RNA. The nucleocapsids had sedimenation coefficients of 115S, 90S, and 65S. Negative-contrast electron microscopy of the nucleocapsids indicated that they were convoluted, supercoiled, and apparently circular. They had a mean diameter of 10 to 12 nm and modal lengths of 200, 510, and 700 nm (some were even longer). By chemical and enzymatic analysis of purified viral RNA, one type of 5' nucleotide (pppAp) present in the proportion of one per RNA segment was identified. After periodate oxidation, each virion RNA species was labeled by reduction with [3H]sodium borohydride. Taken together, these results suggest that although the nucleocapsids appear as closed loops, the viral RNA has free 5' and 3' ends and is, therefore, not circular.

Capsid↗
PubMed1976

Early lymphoreticular viral tropism and antigen persistence. Tamiami virus infection in the cotton rat.

Tamiami virus was inoculated into its natural reservoir host, the cotton rat (Sigmodon hispidus), and the course of infection was followed by sequential organ titrations, frozen-section immunofluorescence, and light and electron microscopy. In animals infected at 2 days of age, there was an early lymphoreticular tropism with peak concentrations of virus and viral antigen in lymph nodes, splenic white pulp, thymus, and bone marrow at 16 days postinoculation. Megakaryocyte infection was early and pronounced. Viral antigen concentration peaked in liver and salivary glands at day 30 and in kidney, adrenal cortex, respiratory tract, and bladder epithelium at day 60-long after viral infectivity in these organs had disappeared. Central nervous system infection was only modestly productive of infectious virus, but viral antigen continued to increase in the brain until day 90 and then did not decline throughout the 360-day study. Reticuloendothelial hyperplastic foci were found late in some target organs, but there was never any histologic or ultrastructural evidence of cytonecrosis. Older animals were virtually uninfectable; therefore, this susceptibility of newborns and their slow termination of infection represent the key to virus transmission and perpetuation in nature. These aspects of viral natural history contribute to an understanding of human exposure to the pathogenic arenaviruses which exist in similar rodent niches.

Age Factors↗
PubMed1976

Lymphoreticular and myeloid pathogenesis of Venezuelan equine encephalitis in hamsters.

Ultrastructural, histopathologic, and virologic studies of adult hamsters infected with virulent Venezuelan equine encelphalomyelitis (VEE) virus (Subtype I-B) demonstrated precise chronologic and topographic progression of lesions and viral replication in extraneural sites. Thymus contained the earliest lesions and the highest initial and subsequent viral titers. No particular cytotropism was observed as highly efficient viral replication and severe cytonecrosis proceded. Early cortical necrosis of splenic periarteriolar lymphocytic sheath was followed by lymphoblastoid repopulation of the peripheral zone. Massive bone marrow necrosis was accompained by ultrastructural evidence of VEE viral particle production in reticulum cells, rubricytes, myeloid cells, lymphoblastoid cells, and megakaryocytes. Speed, efficiency, destructiveness, and relative sensitivity of virtually all lymphoreticular and hematopoetic cells were hallmarks of virulent VEE infection in the hamster.

Animals↗
PubMed1975

Murine oncornavirus activation in the pancreas during infection with Venezuelan equine encephalitis virus.

Electron microscopic studies of the pancreases of 3-week-old ICR Swiss mice infected with Venezuelan equine encephalitis virus and killed 6 days post inoculation (at which time they were moribund) indicated significantly more type-C particles than were found in uninfected controls. This phenomenon was apparently possible because of the microanatomy of the pancreas, in which interstital spaces allowed accumulation of virus particles.

Animals↗
PubMed1975

Cellular resistance to arbovirus infection.

When an arbovirus enters an arthropod in an infected blood meal, several mechanisms may interact to affect its life cycle and ultimate transmissibility. Intrinsic absolute failure in the establishment of infection must be contrasted with infection that is successfully established but is variably modulated in its viral yield throughout the vector's life-span. Degrees of vertebrate host resistance make this modulation a central factor in determining whether an arthropod is an important vector in nature; moreover, human intervention that affects modulating mechanisms may become a basis for disease control. In the absence of evidence of real immune resistance to arbovirus infections in arthropods, other more primitive modulating mechanisms must be considered: interferonlike substances may be formed in arthropod cells; arthropod cells may "cure" themselves by a unique endophagocytic digestion of their virus burden; homologous interference with viral replicative processes may be mediated via wild or mutant viral RNA species acting to shut down further RNA synthesis; and homologous interference may be mediated by RNA of defective-interfering virus formed earlier in infection.

Aedes↗
PubMed1975

Relationship of two arthropod-borne rhabdoviruses (kotonkan and Obodhiang) to the rabies serogroup.

Indirect immunofluorescence confirmed the antigenic relationship between kotankan and Obodhiang viruses and Mokola virus that had originally been shown by complement fixation test. This relationship suggests inclusion of these two arthropod isolates in the rabies subgroup of the Rhabdoviridae family. Cross-reactivity with Mokola virus was also demonstrated by direct immunofluorescence but was easily eliminated when conjugates were diluted. No crossreactivities were found by neutralization tests or by surface immunofluorescence. Other than these immunological ties to the rabies serogroup, other biological characteristics of kotonkan and Obodhiang viruses were distinct. Maximum yield of infectivity of kotonkan and Obodhiang in cell culture was at 30 C, antigen usually filled the cytoplasm of infected cells diffusely, and syncytia were formed before severe cytonecrosis. By electron microscopy, virus particles and their nucleocapsids appeared cone shaped (mean lengths: kotonkan, 182 nm; Obodhiang, 170 nm). Viral morphogenesis took place on plasma membranes of cells in culture, mouse brain neurons, and inflammatory cells (macrophages) in brain lesions. All of these characteristics of the two viruses, and the known association of kotonkan virus with an acute, febrile illness of cattle in Nigeria, suggest a biological relationship with bovine ephemeral fever virus. The latter is known to exist in the same geographic area but exhibits no serological cross-reaction with either kotonkan or Obodhiang virus. The question of whether these two viruses deserve placement in an expanded rabies subgroup (at the cost of a less precise definition of the subgroup) or in a separate subgroup (which would include bovine ephemeral fever virus) of the Rhabdoviridae family will only be answered by further physicochemical characterization and comparison.

Animals↗
PubMed1975

Experimental Lassa virus infection in the squirrel monkey.

Experimental Lassa virus infection was investigated in a nonhuman primate in order to elucidate the target organs of the viral infection and the course of pathologic events. Four squirrel monkeys (Saimiri scirreus) were inoculated intramuscularly with Lassa virus and sacrificed for organ titrations and histopathology, one each day, on Days 7, 12, 14, and 28 after inoculation. The animals showed a variable clinical course, with an incubation period of 8 to 18 days. The virus was demonstrated to be virtually pantropic; however, lymph node, liver, and kidney were key early targets. After the onset of overt disease, patterns of lymphoreticulotropism, hepatotropism, nephrotropism, adrenotropism, and persistent viremia were evident. Complement-fixing antibody failed to develop after 28 days of infection. Histopathologic findings included germinal center necrosis in spleen and lymph node; myocarditis; acute arteritis; renal tubular necrosis and regeneration; hepatocytic regeneration; chronic inflammation of choroid plexus, ependyma, and meninges; and cerebral perivascular cuffing. There is a relationship between many of these lesions and certain features of other arenavirus infections. The model offers the opportunity to pursue investigations of experimental pathogenesis, transmissibility, and efficacy of immunotherapy.

Animals↗
PubMed1975

Lassa virus hepatitis. Observations on a fatal case from the 1972 Sierra Leone epidemic.

During a recent outbreak of Lassa fever in Sierre Leone, a 20-year-old woman developed an acute febrile disease with tonsillar exudates and hemorrhagic manifestations. Lassa virus was isolated in cell cultures from pharyngeal secretions and pleural fluid and was identified by complement fixation. Typical arenavirus particles were observed in these infected cell cultures. In a liver biopsy specimen, diffuse hepatocellular damage and focal necroses were evident, with a spectrum of liver cell change, ranging from slight vacuolizaiton to frank lysis. Virus was frequently observed in nearby extracellular spaces and was clearly associated with hepatocytes rather than sinusoidal cells. The demonstration for the first time of Lassa virus particules in human tissue provides direct evidence that the virus is responsible for the observed pathologic changes.

Disease Outbreaks↗
PubMed1975

Arenavirus taxonomy: a review.

Despite a late beginning, the construction of the arenavirus taxon and its placement in the scheme of the International Committee on Taxonomy of Viruses has now been completed. The bringing together of the member viruses has already provided valuable indications of promising laboratory and field study approaches; in the future this classification will contribute further to our understanding of the natural history and disease processes of the human pathogens of the group.

Arboviruses↗
PubMed1975

Morphology and morphogenesis of arenaviruses.

Arenaviruses have unique structural characteristics; they are pleomorphic, have a mean diameter of 110-130 nm, and consist of a membranous envelope with surface projections surrounding an interior containing ribosomes and filaments. Virus particles bud from plasma membranes of infected cells and in many cases large intracytoplasmic inclusion bodies are formed. These characteristics allow generic identification, but not differentiation of individual viruses. Ultrastructural identification of virus particles and pathological processes in infected tissues of man and experimental animals is important in understanding the nature of arenaviral pathogenesis Such identification also contributes to our understanding of the mechanisms of viral shedding and transmission in reservoir host species.

Animals↗
PubMed1975

Tamiami virus infection in mice and cotton rats.

Tamiami virus produces a lethal encephalitis in suckling mice, and the illness is mediated, at least in part, by cellular immunity. Infection of extraneural organs, including lymphoid organs, is limited. The same virus produces a widespread infection in its natural host, the cotton rat, but neither symptomatic illness nor cytopathology results. Since antibody is produced, as in the murine infection, suppression of cellular immunity to the virus may be responsible for the non-cytolytic infection. Lymphoid tissue is extensively infected in the cotton rat and a relationship between this lymphotropism and immunosuppression is suggested.

Animals↗
PubMed1975

Comparative pathology of Lassa virus infection in monkeys, guinea-pigs, and Mastomys natalensis.

Experimental Lassa virus infections of squirrel monkeys, guinea-pigs, and the African multimammate rat, Mastomys natalensis, were studied virologically and pathologically. In the monkeys, early viral lymphoreticulotropism, hepatotropism, nephrotropism, and viraemia were noted. At the time of death, viral titres in nearly all target organs were associated with necrotic changes: splenic lymphoid necrosis, renal tubular necrosis, myocarditis, arteritis, and hepatocytic regeneration. In convalescent monkeys, organ titres diminished slowly, and viraemia persisted at 28 days. At this time, renal and splenic regeneration was occurring and a new lesion, choriomeningitis, was present.Guinea-pigs infected with Lassa virus developed respiratory insufficiency with pulmonary oedema, alveolar hyaline membranes, myocarditis, and focal calcification of myocardial fibres and hepatocytes. Dying animals contained Lassa virus in virtually every organ tested, whereas survivors at 56 days were free of virus and had high complement-fixing antibody titres.Infection of neonatal Mastomys did not cause any clinical disease or pathological lesions despite the presence of virus in the blood, lymph nodes, liver, spleen, lung, brain, urine, and throat secretions throughout the 74-day study. Infected adult Mastomys also remained normal but had virus in many organs. In one animal, virus persisted until the termination of the study at 103 days. Several animals developed a mild meningoencephalitis. The pattern of infection and virus shedding in M. natalensis is ideal for maintenance of the virus in nature; together with the epidemiological field data this emphasizes the incidental nature of the exposure and infection of man.

Animals↗