UNIVERSITY OF VERMONT AND STATE AGRICULTURAL COLLEGE
发明人:
BRUCE, Emily Adaline,BOTTEN, Jason William,ZIEGLER, Christopher Michael
申请号：
USUS2017/021390
公开号：
WO2017/156146A1
申请日:
2017.03.08
申请国别(地区):
WO
年份:
2017
代理人:
摘要：
Provided are modified arenaviruses and populations thereof, wherein the modified arenaviruses include i) an introduced PPXY domain ii) an increased number of PPXY domains iii) a substituted amino acid in place of S41 in a viral Z protein that is not a substrate for a serine or tyrosine kinase, or a combination of i)-iii). A PPXY domain can include a phosphomimetic replacement of the Y amino acid. Modified Old World and New World arenaviruses are included. Arenavirus production is provided using cell cultures that contain a kinase inhibitor that inhibits a kinase that can phosphorylate the Y amino acid of the PPXY domain, or by cells that have disrupted kinase gene expression, or by cells that have a disrupted ESCRT system. Also provided are pharmaceutical formulations that contain modified arenaviruses, and methods of using such formulations for stimulating an immune response hat is fully or partially protective against arenavirus infection. Also provided is a method for producing a population of arenaviruses that involves culturing cells that i) are infected with a wild type arenavirus, or ii) comprise one or more expression vectors encoding the arenavirus, wherein the cells are characterized by at least one of: a) comprising kinase inhibitor or b) a modification such that expression of a kinase capable of phosphorylating a tyrosine in a PPXY domain of the arenavirus is inhibited or eliminated, or c) a disrupted ESCRT pathway.Linvention concerne des arénavirus modifiés et des populations de ces derniers, les arénavirus modifiés comprenant i) un domaine PPXY introduit ii) un nombre plus grand de domaines PPXY iii) un acide aminé substitué à la place de S41 dans une protéine Z virale qui nest pas un substrat pour une sérine ou une tyrosine kinase, ou une combinaison des modifications i) à iii). Un domaine PPXY peut comprendre un remplacement phosphomimétique de lacide aminé Y. Linvention concerne des arénavirus de lAncien monde modifiés et des arénavirus du Nouveau
