A5072936149- Viral Infections and Outbreaks Research
- HIV Research and Treatment
- Viral gastroenteritis research and epidemiology
- Viral Infections and Vectors
- HIV/AIDS drug development and treatment
- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- Herpesvirus Infections and Treatments
- T-cell and B-cell Immunology
- vaccines and immunoinformatics approaches
- Mosquito-borne diseases and control
- Biochemical and Molecular Research
- Animal Virus Infections Studies
- Acute Lymphoblastic Leukemia research
- Influenza Virus Research Studies
- T-cell and Retrovirus Studies
- Virology and Viral Diseases
- Glycosylation and Glycoproteins Research
- RNA and protein synthesis mechanisms
- Synthesis and Biological Evaluation
- Molecular Biology Techniques and Applications
- Plant Virus Research Studies
- Animal Disease Management and Epidemiology
University of Montana
2009-2024
Cornell University
2001-2002
Howard Hughes Medical Institute
1999
New York University
1999
United States Military Academy
1991-1994
Merck & Co., Inc., Rahway, NJ, USA (United States)
1991-1992
Adamas Pharmaceuticals (United States)
1984
Yale University
1982
Stanford University
1978-1980
Methotrexate-resistant Chinese hamster ovary cells selected for high resistance by progressive increments of methotrexate in the culture medium have levels dihydrofolate reductase (tetrahydrofolate dehydrogenase, 7,8-dihydrofolate: NADP+ oxidoreductase, EC 1.5.1.3) 200 times that sensitive and a corresponding increase number copies gene. The resistant contain an expanded region on second chromosome (homogeneously staining region) is not present cells. In situ hybridization DNA complementary...
Human immunodeficiency virus type 1 (HIV-1)-specific pyridinone reverse transcriptase (RT) inhibitors prevent HIV-1 replication in cell culture (M. E. Goldman, J. H. Nunberg, A. O'Brien, J.C. Quintero, W. Schleif, K. F. Freund, S. L. Gaul, Saari, Wai, M. Hoffman, P. Anderson, D. Hupe, Emini, and Stern, Proc. Natl. Acad. Sci. USA 88:6863-6867, 1991). In contrast to nucleoside analog inhibitors, such as AZT, which need be converted triphosphates by host cells, these compounds act directly...
Derivatives of pyridinones were found to inhibit human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) activity and prevent the spread HIV-1 infection in cell culture without an appreciable effect on other retroviral or cellular polymerases. 3-[( (4,7-Dimethyl-1,3-benzoxazol-2-yl) methyl]amino ]-5-ethyl-6-methylpyridin-2(1H)-one (L-697,639) 3-[[ (4,7-dichloro-1,3-benzoxazol-2-yl) methyl]amino]-5-ethyl-6-methylpyridin-2(1H)-one (L-697,661), two compounds within this series,...
A methotrexate (MTX)-resistant murine lymphoblastoid cell line has been obtained by serial passage in increasing concentrations of MTX which is greater than 100,000-fold resistant to (L5178YR) and dihydrofolate reductase (DHFR) levels 300-fold higher the parental line. The L5178YR synthesizes approximately 10-11% its total soluble protein as DHFR regardless growth phase, measured direct immunoprecipitation with a monospecific antiserum. Molecular hybridization purified [3H]DNA probe...
The filamentous ascomycete Aspergillus awamori secretes large amounts of glucoamylase upon growth in medium containing starch, glucose, or a variety hexose sugars and sugar polymers. We examined the mechanism this carbon source-dependent regulation accumulation found several hundredfold increase mRNA cells grown on an inducing substrate, relative to noninducing xylose. postulate that induction synthesis is regulated transcriptionally. Comparing total from starch xylose, we were able identify...
Arenaviruses comprise a diverse family of rodent-borne viruses that are responsible for recurring and emerging outbreaks viral hemorrhagic fevers worldwide. The Junín virus, member the New World arenaviruses, is endemic to pampas grasslands Argentina etiologic agent Argentine fever. In this study, we have analyzed assembly function virus envelope glycoproteins. mature glycoprotein complex proteolytically processed from GP-C precursor polypeptide consists three noncovalently associated...
Seven diverse primary isolates of human immunodeficiency virus type 1 (HIV-1) were examined and found to be refractory neutralization by antisera recombinant gp120 (rgp120) protein from HIV-1 MN. This stands in marked contrast the sensitivity exhibited certain laboratory-adapted viruses. To understand difference between viruses, we adapted ACH 168.10 growth FDA/H9 cell line. was chosen because V3 region closely matches that After 4 weeks, infection became evident. The (168A) replicated cells...
The envelope glycoprotein of the arenaviruses (GP-C) is unusual in that mature complex retains cleaved, 58-amino-acid signal peptide. Association this stable peptide (SSP) has been shown to be essential for intracellular trafficking and proteolytic maturation GP-C complex. We identify here a specific previously unrecognized role SSP pH-dependent membrane fusion. Amino acid substitutions alter positive charge at lysine K33 affect ability mediate cell-cell fusion threshold pH which triggered....
Interleukin 2 (IL-2) occupies a central position in the cascade of events involved immune response. We were interested determining whether IL-2 could function as an adjuvant to vaccination, increase response vaccine immunogens. Using National Institutes Health test for rabies potency, we found that daily systemic administration conjunction with inactivated virus can potency vaccination outbred mice at least 25-fold, measured by survival following challenge virulent virus. Enhanced protection...
ABSTRACT A number of New World arenaviruses (Junín [JUNV], Machupo [MACV], and Guanarito [GTOV] viruses) can cause human disease ranging from mild febrile illness to a severe often fatal hemorrhagic fever syndrome. These highly pathogenic viruses the Old Lassa virus pose significant threat public health national security. The only licensed antiviral agent with activity against these viruses, ribavirin, has had mixed success in treating arenaviral is associated toxicities. novel pyrazine...
ABSTRACT The arenavirus envelope glycoprotein (GPC) mediates viral entry through pH-induced membrane fusion in the endosome. This crucial process life cycle can be specifically inhibited New World arenaviruses by small-molecule compound ST-294. Here, we show that ST-294 interferes with GPC-mediated targeting interaction of G2 subunit stable signal peptide (SSP). We demonstrate amino acid substitutions at lysine-33 Junín virus SSP confer resistance to and engender de novo sensitivity ST-161,...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT2-Pyridinone derivatives: a new class of nonnucleoside, HIV-1-specific reverse transcriptase inhibitorsWalfred S. Saari, Jacob M. Hoffman, John Wai, Thorsten E. Fisher, Clarence Rooney, Anthony Smith, Craig Thomas, Mark Goldman, Julie A. O'Brien, and Cite this: J. Med. Chem. 1991, 34, 9, 2922–2925Publication Date (Print):September 1, 1991Publication History Published online1 May 2002Published inissue 1 September...
Feline herpesvirus 1 (FHV) is the causative agent of viral rhinotracheitis in cats. Current vaccination programs employing attenuated live and killed FHV vaccines have been effective reducing incidence this disease. As an initial step development recombinant FHVs for use cats, we identified thymidine kinase (TK) gene feline-specific alphaherpesvirus. Comparisons amino acid sequences other TK proteins shown that these are highly divergent, sharing only short regions imperfect identity. We...
Arenaviruses are responsible for acute hemorrhagic fevers with high mortality and pose significant threats to public health biodefense. These enveloped negative-sense RNA viruses replicate in the cell cytoplasm express four proteins. To better understand how these proteins insinuate themselves into cellular processes orchestrate productive viral replication, we have identified characterized novel cytosolic structures involved arenavirus replication transcription. In cells infected...