Universitéde Montreal

Other

Eric A Cohen

Dominique Bergeron

Xiao-Jian Yao

Gary Pignac-Kobinger

Florent Checroune

Paul Brazeau

Yves Langelier

Pierrette Gaudreau

Jacques Michaud

Andrew J Mouland

Louise Wickham

Ming Luo

Thomas Duchaîne

The present invention relates to mammalian staufen, a double-stranded RNA-binding protein involved in mRNA transport and localization. The invention further relates to the demonstration of the association of a RNA-binding protein with the rough endoplasmic reticulum (RER), implicating staufen and related proteins in the transport of RNA to its site of translation. Broadly, the invention therefore relates to transport and translation of RNA. More specifically, the present invention relates to human and mouse staufen proteins and to the modulation of transport of RNA to the RER by these proteins. The present invention also relates to isolated nucleic acid molecules encoding mammalian staufen, as well as vectors and host cells harboring same. In addition, the present invention relates to screening assays for identifying modulators of staufen activity and to the identification of mutants thereof which abrogate their interaction with RER. Furthermore, the present invention relates to the use of the double-stranded RNA binding activity of staufen as a means to target proteins into virions. The invention in addition relates to the incorporation of staufen into RNA viruses and the use of overexpression of staufen to significantly decrease the infectivity thereof. More particularly, the present invention relates to a novel and broad class of molecules which can be used as carriers to target molecules into virions of RNA viruses and to decrease infectivity of a wide variety of RNA viruses including retroviruses.

Mammalian stauffen and use thereof

The present invention relates to a Vpr protein, a Vpx protein or fragments thereof which permit the development of chimeric molecules that can be specifically targeted into the mature HIV-1 and HIV-2 virions to affect their structural organization and/or functional integrity, thereby resulting in gene therapy for HIV-1 and HIV-2 infections. The present invention also relates to Vpr/Vpx protein Fragments, p6 protein, p6 protein fragment, or functional derivatives thereof which interfere with the native Vpr/Vpx incorporation into HIV-1 and HIV-2 virions. The present invention also relates to treatment of HIV-1 and HIV-2 infections based on the proteins of the present invention.

Protein targeting into HIV virions based on HIV-1 VPR fusion molecules

The present invention relates to a Vpr protein, a Vpx protein or fragments thereof which permit the development of chimeric molecules that can be specifically targeted into the mature HIV-1 and HIV-2 virions to affect their structural organization and/or functional integrity, thereby resulting in gene therapy for HIV-1 and HIV-2 infections. The present invention also relates to Vpr/Vpx protein fragments, p6 protein, p6 protein fragment, or functional derivatives thereof which interfere with the native Vpr/Vpx incorporation into HIV-1 and HIV-2 virions. The present invention also relates to treatment of HIV-1 and HIV-2 infections based on the proteins of the present invention.

Expression vectors encoding recombinant proteins comprising a VPR/VPX

The present invention is directed toward chimeric human immunodeficiency virus type 1 and 2 (HIV-1 and -2) proteins that are capable of being incorporated into the virion when expressed in trans. These chimeric proteins consist of a first portion comprising an HIV-1 or HIV-2 Vpr/Vpx virion incorporation domain which includes the predicted N-terminal alpha helix. This domain is capable of interacting with the p6 domain of the Pr55.sup.gag. The second portion of the chimera comprises a sequence containing RNase activity, protease activity, or a domain capable of inhibiting virion morphogenesis and assembly. The disclosed invention provides a chimera that affects the structural organization or functional integrity of the mature virion by enzymatic disturbance or steric hindrance of the virion.

Chimeric proteins comprising a Vpr/Vpx virion incorporation domain for

Disclosed herein are antiviral peptides of the formula A-R.sup.8 -R.sup.9 -R.sup.10 -R.sup.11 -R.sup.12 -R.sup.13 -R.sup.14 -R.sup.15 B wherein A is from zero up to seven amino acid residues and includes a terminal hydrogen or a terminal N-acyl, or A is a phenylpropionyl with optional substitution of the para position of the phenyl, R.sup.8, R.sup.9, R.sup.10, R.sup.13, R.sup.14 and R.sup.15 are various amino acid residues with the stipulation that one or more of the three amino acid residues immediately preceeding R.sup.11 and R.sup.12 are independently Val, D-Val, Nva, D-Nva, Leu, D-Leu, Nle, D-Nle, Ile or D-Ile, and B is hydroxy, amino or lower alkylamino. The antiviral activity of the peptides can be enhanced by combining them with a protease inhibitor. The peptides and the combination are useful for the treatment of herpes viral infections in mammals.

Antiviral peptides and means for treating herpes infections

Disclosed herein are antiviral peptides of the formula A-R.sup.8 -R.sup.9 -R.sup.10 -R.sup.11 -R.sup.12 -R.sup.13 -R.sup.14 -R.sup.15 -B wherein A is from zero up to seven amino acid residues and includes a terminal hydrogen or a terminal N-acyl, or A is a phenylacetyl with optional substitution of the para position of the phenyl, R.sup.8, R.sup.9, R.sup.10, R.sup.13, R.sup.14 and R.sup.15 are various amino acid residues with the stipulation that one or more of the four amino acid residues immediately preceding R.sup.11 may optionally be deleted, R.sup.11 and R.sup.12 are independently Val, D-Val, Nva, D-Nva, Leu, D-Leu, Nle, D-Nle, Ile or D-Ile, and B is hydroxy, amino or lower alkylamino. The antiviral activity of the peptides can be enhanced by combining them with a protease inhibitor. The peptides and the combination are useful for the treatment of herpes viral infections in mammals.

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Montreal, Canada

Eric A Cohen