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F Gonzalez-Scarano

Publications and source records attributed to F Gonzalez-Scarano.

64 records · Page 4Linked to original sources
PubMed1985

La Crosse virus G1 glycoprotein undergoes a conformational change at the pH of fusion.

La Crosse virus, a member of the family Bunyaviridae, can mediate cell-to-cell fusion after mild acidification. Either of its two envelope glycoproteins could potentially be responsible for this function. The large glycoprotein (G1) undergoes a conformational change at the pH of activation of the fusion function, resulting in both an alteration in the cleavage pattern produced by amino-acid-specific proteases, and in a change in its antigenicity, as defined by altered binding of monoclonal antibodies.

Antibodies, Monoclonal↗
PubMed1985

An avirulent G1 glycoprotein variant of La Crosse bunyavirus with defective fusion function.

La Crosse virus, a member of the California serogroup of the family Bunyaviridae, causes encephalitis in humans and laboratory rodents. A variant virus (V22) selected with a monoclonal antibody against the large (G1) glycoprotein showed diminished neuroinvasiveness after peripheral inoculation. This variant has an alteration in its fusion function, requiring a lower pH for the activation of fusion and demonstrating reduced efficiency of cell-to-cell fusion of BHK-21 cultures. V22 was studied in detail following the infection by intraperitoneal or intracerebral routes in suckling, weanling, or adult CD-1 mice. It exhibited a marked reduction in its ability to replicate in striated muscle and to produce viremia; however, after intracerebral injection V22 virus replicated almost as rapidly in brain as its parent, La Crosse virus. V22 virus thus represents an example of reduced neuroinvasiveness associated with an alteration at a specific epitope of the G1 glycoprotein. This same epitope also influences the fusion activity of the glycoprotein.

Animals↗
PubMed1984

La Crosse bunyavirus can mediate pH-dependent fusion from without.

Lipid binding properties which are dependent on exposure to acid pH are an important mechanism for the cellular entry pathway for some enveloped viruses and for other macromolecules. Cell-to-cell fusion can be used to demonstrate this function. La Crosse virus, a member of the family Bunyaviridae, fused BHK-21 cells from without (FFWO) upon exposure of the absorbed virus to pH 6.3 or below. A high multiplicity of infection and temperature of 37 degrees were necessary for optimum fusion. The pH requirement was similar to that reported for Semliki forest virus, an alphavirus, but higher than that required for the demonstration of cell fusion by members of the Orthomyxoviridae. Virus inactivated by ultraviolet light also mediated FFWO. This is the first report of pH-mediated fusion for this family of viruses and it suggests, by analogy with other viruses, that their entry pathway includes exposure to acid.

Animals↗
PubMed1984

Mechanisms of bunyavirus virulence. Comparative pathogenesis of a virulent strain of La Crosse and an avirulent strain of Tahyna virus.

To analyze mechanisms of virulence in the California serogroup bunyaviruses, the virulent La Crosse/original (LAC/original) strain was compared with the avirulent Tahyna/181-57 strain. In suckling mice, both viruses were lethal upon intracerebral injection but differed markedly in their neuroinvasiveness following subcutaneous injection; 20 and 20,000 plaque-forming units, respectively, were equivalent to 1 subcutaneous LD50. The sequential course of infection was followed after subcutaneous injection of 700 plaque-forming units; LAC/original replicated in striated muscle, caused a high titer plasma viremia, invaded the central nervous system, and killed all mice; the same dose of avirulent Tahyna/181-57 failed to replicate in extraneural tissues, did not invade the central nervous system, and caused no apparent illness. Immunofluorescent examination of peripheral and central nervous system tissues showed the same distinctions between virulent and avirulent viruses and pinpointed striated muscle as the major extraneural target of virulent LAC/original virus. Paradoxically, after intracerebral injection of suckling or adult mice, Tahyna/181-57 virus killed more quickly than LAC/original. This difference was correlated with replication differences; Tahyna/181-57 multiplied marginally faster in the brain than did LAC/original virus.

Aging↗
PubMed1983

Monoclonal antibodies against the G1 and nucleocapsid proteins of LaCrosse and Tahyna viruses.

Monoclonal antibodies against the Gl (glycoprotein) and Nc (nucleocapsid) proteins of LaCrosse (LAC) and Tahyna (TAH) viruses were generated using a standard protocol. Monoclonal antibodies against Gl were either neutralizing or non-neutralizing, and there was close concordance between inhibition of hemagglutination and neutralizing activities. The LAC virus neutralizing antibodies could be further subdivided into strain-specific and cross-reactive groups on the basis of both neutralization and inhibition of hemagglutination. These data support the concept of a glycoprotein molecule with three antigenic sites, two involved in neutralization and hemagglutination, and an additional site with no biological function as yet defined. Preliminary information from LAC virus variants selected with these monoclonal antibodies agrees with this interpretation. Anti Nc antibodies were all cross-reactive in an ELISA assay. Patterns of monoclonal cross-reactivity against California serogroup viruses are compared with the currently accepted antigenic relationships.

Antibodies, Monoclonal↗
PubMed1981

Primary epiduritis.

An infant, born with multiple anomalies of the gastrointestinal tract, required intravenous hyperalimentation for virtually his entire life. His course was characterized by multiple episodes of sepsis or phlebitis, culminating in death five and one-half months after birth. The brain and spinal cord at necropsy were normal on gross inspection. However, microscopic study showed inflammation of the dura surrounding the spinal cord with sparing of the spinal and cerebral subarachnoid spaces.

Digestive System Abnormalities↗
PubMed1979

Cranial computed tomography in the diagnosis of systemic lupus erythematosus.

The cranial computed tomograms of 29 patients with systemic lupus erythematosus (SLE) were reviewed. Twenty-two patients had a clinical course consistent with central nervous system involvement. Of these, 20 had abnormal CT studies during the course of their CNS symptoms. The most common finding was sulcal enlargement, either with or without ventricular enlargement, and it was prominent in patients with either psychosis or dementia. Infarcts and intracranial hemorrhages were seen as well. Seven CT studies were obtained in SLE patients without a clear diagnosis of CNS involvement. Only one of these was abnormal.

Adolescent↗
PubMed1978

Central nervous system immunity in mice infected with theiler's virus. I. Local neutralizing antibody response.

Experimental Theiler's mouse encephalomyelitis virus (TMEV) infection in mice is atypical of most other picornavirus infections because virus persists in the host. It was shown previously that low levels of infectious virus are readily detectable in the central nervous system (CNS) despite the presence of substantial titers of serum neutralizing antibody. In this study antibody assays were performed on CNS tissue homogenates, and neutralizing antibody was regularly found in the CNS of TMEV-infected mice. That neutralization by infected CNS extracts was due to antibody was demonstrated by the specificity of neutralization for TMEV and by elimination or marked reduction of neutralization by in vitro treatment with goat antiserum to mouse IgG. In addition, immunofluorescent staining consistently revealed IgG- but not IgM-containing cells in perivascular cuffs and parenchymal lesions of the brains of infected animals. Evidence of local antibody formation in the CNS was found in the actual reversal of the serum-CNS antibody ratio in about one-third of infected mice after three weeks. In contrast, normal mice had a mean serum-CNS antibody ratio of approximately 100:1 after passive transfer of antibody. Possible reasons for the fact that TMEV is not neutralized by antibody and chronic infection is not aborted include the formation of complexes of infectious virus and antibody in the CNS and the production of antibodies with low affinity for TMEV.

Animals↗
PubMedDate not supplied

MR proton spectroscopy in multiple sclerosis.

PURPOSE: To elucidate the natural history of visualized MR abnormalities in patients with multiple sclerosis using proton spectroscopy. METHODS: MR imaging and proton spectroscopy (1H spectroscopy) were performed on 16 patients with clinically definite multiple sclerosis. All patients received gadopentetate dimeglumine (Gd-DTPA). RESULTS: Decreased levels of N-acetylaspartate (NAA) were demonstrated in 17 out of 21 lesions. No correlation was found between decreased NAA and Gd-DTPA enhancement. In five out of seven enhancing lesions, abnormal 1H spectra with extra peaks (termed marker peaks) at 2.1-2.6 ppm (ranging in absolute concentration from 10-50 mM protons) were observed. In nine out of 14 unenhancing lesions, no elevated marker peaks were observed. In the five other unenhancing lesions, the levels of these marker peaks were generally lower than the enhancing group. No correlation was found between the NAA levels and the levels of the marker peaks. We suggest two distinct biochemical processes: 1) decreased NAA reflecting neuronal cell loss, and 2) elevated marker peaks reflecting ongoing demyelination. CONCLUSIONS: Based upon these observations we infer that 1) the majority of enhancing lesions are demyelinating with extra peaks at 2.1-2.6 ppm representing a marker of this process, 2) enhancing lesions without this marker most likely represent edematous regions without significant demyelination, and 3) demyelination may be long in duration compared with transient blood-brain barrier disruption manifested by Gd-DTPA enhancement. Our results suggest that 1H spectroscopy has the ability to further categorize MR-demonstrated enhancing and unenhancing lesions in patients with multiple sclerosis and that it may be more sensitive than contrast enhancement in revealing the true time course of demyelination.

Adult↗