THE P15 MATRIX PROTEIN OF MOLONEY MURINE LEUKEMIA-VIRUS IS A PHOSPHOTYROSINE PROTEIN

Retroviruses have been etiologically implicated with leukemia in human s and animals. Understanding the virus life cycle, the proteins and en zymes involved in its replication, is essential for developing potent anti-viral drugs, Phosphorylation of retroviral proteins may alter the ir shape in such a way as to increase or inhibit their biological acti vities and thus influence the replication and pathogenic potential of the retroviruses. In our previous work, we demonstrated that non-cytot oxic doses of tyrphostins (protein tyrosine kinase blockers) inhibit m oloney murine leukemia virus (Mo-MuLV) replication in acutely and chro nically infected cells. In an attempt to understand their mode of acti on as anti-MoMuLV drugs, we examined the possibility that a viral prot ein is phosphorylated in tyrosine. Indeed, in our present work, we sho w that the p15 matrix protein (MA) of Mo-MuLV is a phosphotyrosine pro tein and is the only viral protein which is phosphorylated on tyrosine , Moreover, treatment of Mo-MuLV/NIH/ 3T3 chronically infected cells w ith tyrphostin AG-555 specifically inhibits the synthesis of p15 and o ther viral proteins but does not affect the synthesis of cellular prot eins, Our results suggest that tyrosine phosphorylation of p15 MA prot ein may play a pivotal role in Mo-MuLV replication.