Biomedical subjects

Himangi R Jayakar

Publications and source records attributed to Himangi R Jayakar.

4 recordsLinked to original sources

PubMed2004

Rhabdovirus assembly and budding.

Rhabdoviruses are a diverse, widely-distributed group of enveloped viruses that assemble and bud from the plasma membrane of host cells. Recent advances in the identification of domains on both the envelope glycoprotein and the matrix protein of rhabdoviruses that contribute to virus assembly and release have allowed us to refine current models of rhabdovirus budding and to describe in better detail the interplay between both viral and cellular components involved in the budding process. In this review we discuss the steps involved in rhabdovirus assembly beginning with genome encapsidation and the association of nucleocapsid-matrix protein pre-assembly complexes with the inner leaflet of the plasma membrane, how condensation of these complexes may occur, how microdomains containing the envelope glycoprotein facilitate bud site formation, and how multiple forms of the matrix protein may participate in virion extrusion and release.

Animals↗

PubMed2004

Functional analysis of late-budding domain activity associated with the PSAP motif within the vesicular stomatitis virus M protein.

A PPPY motif within the M protein of vesicular stomatitis virus (VSV) functions as a late-budding domain (L-domain); however, L-domain activity has yet to be associated with a downstream PSAP motif. VSV recombinants with mutations in the PPPY and/or PSAP motif were recovered by reverse genetics and examined for growth kinetics, plaque size, and budding efficiency by electron microscopy. Results indicate that unlike the PPPY motif, the PSAP motif alone does not possess L-domain activity. Finally, the insertion of the human immunodeficiency virus type 1 p6 L-domain and flanking sequences into the PSAP region of M protein rescued budding of a PPPY mutant of VSV to wild-type levels.

Amino Acid Motifs↗

PubMed2004

Recombinant vesicular stomatitis virus vectors as oncolytic agents in the treatment of high-grade gliomas in an organotypic brain tissue slice-glioma coculture model.

OBJECT: The purpose of this study was to evaluate both replication-competent and replication-restricted recombinant vesicular stomatitis virus (VSV) vectors as therapeutic agents for high-grade gliomas by using an organotypic brain tissue slice-glioma coculture system. METHODS: The coculture system involved growing different brain structures together to allow neurons from these tissues to develop synaptic connections similar to those found in vivo. Rat C6 or human U87 glioma cells were then introduced into the culture to evaluate VSV as an oncolytic therapy. The authors found that recombinant wild-type VSV (rVSV-wt) rapidly eliminated C6 glioma cells from the coculture, but also caused significant damage to neurons, as measured by a loss of microtubule-associated protein 2 immunoreactivity and a failure in electrophysiological responses from neurons in the tissue slice. Nonetheless, pretreatment with interferon beta (IFNbeta) virtually eliminated VSV infection in healthy tissues without impeding any oncolytic effects on tumor cells. Despite the protective effects of the IFNbeta pretreatment, the tissue slices still showed signs of cytopathology when exposed to rVSV-wt. In contrast, pretreatment with IFNbeta and inoculation with a replication-restricted vector with its glycoprotein gene deleted (rVSV-deltaG) effectively destroyed rat C6 and human U87 glioma cells in the coculture, without causing detectable damage to the neuronal integrity and electrophysiological properties of the healthy tissue in the culture. CONCLUSIONS: Data in this study provide in vitro proof-of-principle that rVSV-deltaG is an effective oncolytic agent that has minimal toxic side effects to neurons compared with rVSV-wt and therefore should be considered for development as an adjuvant to surgery in the treatment of glioma.

Animals↗

PubMed2002

Identification of two additional translation products from the matrix (M) gene that contribute to vesicular stomatitis virus cytopathology.

The matrix (M) protein of vesicular stomatitis virus (VSV) is a multifunctional protein that is responsible for condensation of the ribonucleocapsid core during virus assembly and also plays a critical role in virus budding. The M protein is also responsible for most of the cytopathic effects (CPE) observed in infected cells. VSV CPE include inhibition of host gene expression, disablement of nucleocytoplasmic transport, and disruption of the host cytoskeleton, which results in rounding of infected cells. In this report, we show that the VSV M gene codes for two additional polypeptides, which we have named M2 and M3. These proteins are synthesized from downstream methionines in the same open reading frame as the M protein (which we refer to here as M1) and lack the first 32 (M2) or 50 (M3) amino acids of M1. Infection of cells with a recombinant virus that does not express M2 and M3 (M33,51A) resulted in a delay in cell rounding, but virus yield was not affected. Transient expression of M2 and M3 alone caused cell rounding similar to that with the full-length M1 protein, suggesting that the cell-rounding function of the M protein does not require the N-terminal 50 amino acids. To determine if M2 and M3 were sufficient for VSV-mediated CPE, both M2 and M3 were expressed from a separate cistron in a VSV mutant background that readily establishes persistent infections and that normally lacks CPE. Infection of cells with the recombinant virus that expressed M2 and M3 resulted in cell rounding indistinguishable from that with the wild-type recombinant virus. These results suggest that M2 and M3 are important for cell rounding and may play an important role in viral cytopathogenesis. To our knowledge, this is first report of the multiple coding capacities of a rhabdovirus matrix gene.

Animals↗