Biomedical subjects

Michael Garbutt

Publications and source records attributed to Michael Garbutt.

7 recordsLinked to original sources

PubMed2004

Genotyping of measles virus in Canada: 1979-2002.

Genotyping is an important component of measles surveillance. In this study, we report the genotypes of 30 measles viruses from cases in Canada; 6 of these were collected between 1979 and 1996 and 24 were collected from 1997 through 2002. Many measles virus genotypes were found (C1, C2, D3, D4, D5, D6, D7, D8, E, and H1). These data indicate that the predominant measles virus genotypes detected from 1979 to 1997 in Canada are no longer commonly found. Since the implementation of a routine second dose of measles vaccine and catch-up campaigns in 1996-1997, the wide variety of measles virus genotypes found supports epidemiological data showing that importation of measles is the source of current measles cases in Canada.

Canada↗

PubMed2004

Properties of replication-competent vesicular stomatitis virus vectors expressing glycoproteins of filoviruses and arenaviruses.

Replication-competent recombinant vesicular stomatitis viruses (rVSVs) expressing the type I transmembrane glycoproteins and selected soluble glycoproteins of several viral hemorrhagic fever agents (Marburg virus, Ebola virus, and Lassa virus) were generated and characterized. All recombinant viruses exhibited rhabdovirus morphology and replicated cytolytically in tissue culture. Unlike the rVSVs with an additional transcription unit expressing the soluble glycoproteins, the viruses carrying the foreign transmembrane glycoproteins in replacement of the VSV glycoprotein were slightly attenuated in growth. Biosynthesis and processing of the foreign glycoproteins were authentic, and the cell tropism was defined by the transmembrane glycoprotein. None of the rVSVs displayed pathogenic potential in animals. The rVSV expressing the Zaire Ebola virus transmembrane glycoprotein mediated protection in mice against a lethal Zaire Ebola virus challenge. Our data suggest that the recombinant VSV can be used to study the role of the viral glycoproteins in virus replication, immune response, and pathogenesis.

Animals↗

PubMed2003

New insights into the evolutionary relationships between arenaviruses provided by comparative analysis of small and large segment sequences.

Arenaviruses are rodent-borne negative-stranded bisegmented RNA viruses. Five arenaviruses are etiologic agents of hemorrhagic fever in humans and are potential agents of bioterrorism. They are classified as Biosafety level 4 agents and listed in the category A of the Pathogen Agents edited by the Center for Disease Control and Prevention. To date, evolution and phylogeny of arenaviruses have been based on the analysis of sequences derived from structural genes (small RNA segment) exclusively, due to the lack of sequences available for the large RNA segment. In this study, partial sequences of the polymerase gene were determined for 18 species of arenaviruses and used to investigate phylogenetic relationships. Comparative analysis of topologies obtained from polymerase and structural gene analyses permitted us to determine the evolutionary origin of the major parent of the North American recombinant arenaviruses, and to investigate the role of genetic exchange (reassortment and recombination) in the evolutionary mechanisms driving the evolution of the genus Arenavirus.

Arenaviruses, New World↗

PubMed2003

Structure of replicating intermediates of human herpesvirus type 6.

We have studied the structure of the replicative intermediates of human herpesvirus 6 (HHV-6) using pulsed-field gel electrophoresis, partial digestion, two-dimensional gel electrophoresis, and sedimentation centrifugation. The results show that DNA replication of HHV-6 produces head-to-tail concatemeric intermediates as well as approximately equal amounts of circular monomers or oligomers. Unlike the situation in herpes simplex virus, the intermediates of human herpesvirus 6 replication are not highly branched, suggesting a difference in the mechanism of replication or a lower frequency of homologous recombination in human herpesvirus 6 compared to herpes simplex virus.

Cell Line↗

PubMed2003

The Genome sequence of the SARS-associated coronavirus.

We sequenced the 29,751-base genome of the severe acute respiratory syndrome (SARS)-associated coronavirus known as the Tor2 isolate. The genome sequence reveals that this coronavirus is only moderately related to other known coronaviruses, including two human coronaviruses, HCoV-OC43 and HCoV-229E. Phylogenetic analysis of the predicted viral proteins indicates that the virus does not closely resemble any of the three previously known groups of coronaviruses. The genome sequence will aid in the diagnosis of SARS virus infection in humans and potential animal hosts (using polymerase chain reaction and immunological tests), in the development of antivirals (including neutralizing antibodies), and in the identification of putative epitopes for vaccine development.

3' Untranslated Regions↗

PubMed2002

Emerging and re-emerging infectious diseases.

In human history, numerous infectious diseases have emerged and re-emerged. Aside from many others, the so-called 'exotic' agents in particular are a threat to our public health systems due to limited experience in case management and lack of appropriate resources. Many of these agents are zoonotic in origin and transmitted from animals to man either directly or via vectors. The reservoirs are often infected subclinically or asymptomatically and the distribution of the diseases basically reflects the range and the population dynamics of their reservoir hosts. As examples, emergence/re-emergence is discussed here for diseases caused by filoviruses, hantaviruses, paramyxoviruses, flaviviruses and Yersinia pestis. In addition, bioterrorism is addressed as one factor which has now to be considered in infectious disease emergence/re-emergence. Preparedness for known and unknown infectious diseases will be a top priority for our public health systems in the beginning of the millennium.

Animals↗

PubMed2002

Cell-permeable ceramides preferentially inhibit coated vesicle formation and exocytosis in Chinese hamster ovary compared with Madin-Darby canine kidney cells by preventing the membrane association of ADP-ribosylation factor.

Differential effects of acetyl(C2-) ceramide (N-acetylsphingosine) were studied on coated vesicle formation from Golgi-enriched membranes of Chinese hamster ovary (CHO) and Madin-Darby canine kidney (MDCK) cells. C2-ceramide blocked the translocation of ADP-ribosylation factor-1 (ARF-1) and protein kinase C-alpha (PKC-alpha) to the membranes from CHO cells, but not those of MDCK cells. Consequently, C2-ceramide blocked the stimulation of phospholipase D1 (PLD1) by the cytosol and guanosine 5'-[gamma-thio]triphosphate (GTP[S]) in membranes from CHO cells. Basal specific activity of PLD1 and the concentration of ARF-1 were 3-4 times higher in Golgi-enriched membranes from MDCK cells compared with CHO cells. Moreover, PLD1 activity in MDCK cells was stimulated less by cytosol and GTP[S]. PLD2 was not detectable in the Golgi-enriched membranes. Incubation of intact CHO cells or their Golgi-enriched membranes with C2-ceramide also inhibited COP1 vesicle formation by membranes from CHO, but not MDCK, cells. Specificity was demonstrated, since dihydro-C2-ceramide had no significant effect on ARF-1 translocation, PLD1 activation or vesicle formation in membranes from both cell types. C2-ceramide also decreased the secretion of virus-like particles to a greater extent in CHO compared with MDCK cells, whereas dihydro-C2-ceramide had no significant effect. The results demonstrate a biological effect of C2-ceramide in CHO cells by decreasing ARF-1 and PKC-alpha binding to Golgi-enriched membranes, thereby preventing COP1 vesicle formation.

ADP-Ribosylation Factors↗