Biomedical subjects

G Lemay

Publications and source records attributed to G Lemay.

57 records · Page 4Linked to original sources

PubMedDate not supplied

Protein synthesis in different cell lines infected with orthoreovirus serotype 3: inhibition of host-cell protein synthesis correlates with accelerated viral multiplication and cell killing.

In this study, we examined the viral multiplication of human reovirus serotype 3 in mammalian cell lines of different species and tissue origins. All cell lines supported viral multiplication to a similar extent, although the kinetics was significantly different in some of these lines. The appearance of infectious virus was delayed in few cell lines. These cell lines also exhibited a much slower rate of cell killing, and in contrast to the others, did not exhibit an inhibition of the synthesis of host-cell proteins. We conclude that the inhibition correlates with rapid cell killing and viral multiplication, while being unrelated to efficient total viral production.

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PubMedDate not supplied

Two basic motifs of reovirus sigma 3 protein are involved in double-stranded RNA binding.

It has been reported that the sigma 3 protein of reovirus can exert an inhibitory effect on the cellular double-stranded RNA (dsRNA) activated protein kinase. Activation of this kinase is thought to be a general mechanism mediating a cellular antiviral response. This enzyme can also be activated upon transfection, resulting in translational inhibition of plasmid-encoded mRNAs. sigma 3 has an affinity for dsRNA postulated to be responsible for antikinase activity. In the present study, site-directed mutagenesis was performed on two basic regions previously suggested as dsRNA-binding motifs and the mutant sigma 3 proteins were then expressed in COS cells. These experiments revealed that both motifs are involved in sigma 3 attachment to RNA. Expression of the mutants lacking RNA-binding capability is stimulated by coexpression of another dsRNA-binding protein, the E3L vaccinia virus protein. These results support a model in which the attachment to dsRNA is directly responsible for the trans-stimulating effect of sigma 3 on expression of cotransfected genes.

Amino Acid Sequence↗

PubMedDate not supplied

Influence of human immunodeficiency virus type 1 envelope glycoprotein YXXL endocytosis/polarization signal on viral accessory protein functions.

INTRODUCTION: A tyrosine-based targeting signal in the intracytoplasmic domain of human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein is required for basolateral targeting of viral budding in polarized epithelial cells, concentration of viral assembly at one pole of infected lymphocytes, and rapid endocytosis of the glycoprotein from the plasma membrane. In HIV-1, the process of viral assembly and budding is complex and involves the participation of viral accessory proteins. STUDY DESIGN/METHODS: In this study, we examined whether the functions of the Nef, Vif, and Vpu proteins can influence or be influenced by the presence of envelope targeting signal in epithelial cells or lymphocytes. A series of proviral DNAs combining a mutation that inactivates the targeting signal with independent mutations in the three accessory proteins was constructed for this purpose. RESULTS: It was found that none of these three accessory proteins affected the basolateral release of the virus in polarized MDCK cells. Reciprocally, a mutation abolishing targeting of the viral envelope glycoprotein did not affect the phenotype conferred by the accessory proteins. Interestingly, the mutation abolishing targeting increased viral infectivity only in the presence of the Vpu protein. This phenotype was found to be associated with the release-enhancing function of Vpu and with an increased incorporation of viral envelope glycoprotein in virions. CONCLUSIONS: These data clearly show that accessory protein functions, and more specifically Vpu modulation of viral infectivity, can be affected by variations in the viral envelope glycoprotein.

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