Comparative processing of bovine leukemia virus envelope glycoprotein gp72 by subtilisin/kexin‐like mammalian convertases

FEBS Letters

Burny, Arsène¹  Wattiez, Ruddy²  Ruysschaert, Jean-Marie³  Zarkik, Sarra³  Decroly, Etienne³  Seidah, Nabil G² 

[1] Laboratoire de Chimie Biologique CP300, Université Libre de Bruxelles, 67, Rue des Chevaux, Rhode Saint-Genèse, Belgium;Service de Chimie Biologique, Université de Mons-Hainaut, Ave. Maistriau 21, 7000 Mons, Belgium;Laboratoire de Chimie Physique des Macromolécules aux Interfaces (LCPMI) CP206/2, Université Libre de Bruxelles, 1050 Brussels, Belgium

关键词: Furin-like;    Bovine leukemia virus;    Envelope glycoprotein;    Dibasic residue;    gp72;    gp51;    gp30;    Convertase;    Processing;    B-lymphocytes;    VV;    vaccinia virus;    PC;    precursor convertase;    RT-PCR;    reverse transcriptase polymerase chain reaction;    BLV;    bovine leukemia virus;    gp;    glycoprotein;    WT;    wild type;    PBS;    phosphate buffer saline;    BSA;    bovine serum albumin;   

DOI  :  10.1016/S0014-5793(97)00275-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Intracellular proteolytic processing of bovine leukemia virus (BLV) envelope glycoprotein precursor (gp72) at the C-terminal end of the RVRR²⁶⁸↓ site is an essential step for virus infectivity. Subtilisin/kexin-like convertases cleave proproteins at preferred RX(K/R)R↓ sites, including those commonly found in viral envelope glycoprotein precursors. We first demonstrated that gp72 is processed into gp51/gp30 in both CV1 cells and the furin-deficient LoVo cells, leading us to compare the ability of mammalian convertases to cleave BLV gp72 in vitro. In contrast to the inability of the neuroendocrine PC1 to cleave gp72, the convertases furin, PACE4, PC5-A and PC5-B, which process constitutively secreted precursors, can effectively cleave gp72 into gp51/gp30. N-terminal sequence analysis of the convertase-generated gp30 demonstrated that cleavage occurs at the in vivo-utilized RVRR↓SPV site. Such furin-, PACE4- and PC5-mediated processing was completely inhibited by the α₁-antitrypsin variant α1-PDX. Mutagenesis of the gp72 cleavage site into RVR - PV resulted in complete abrogation of gp72 processing by endogenous CV-1 cells and by convertases in vitro. Since our in vitro data suggest a redundancy in the ability of the convertases to cleave gp72, RT-PCR analysis was used to define the convertases expressed in B-lymphocytes, representing one of the major targets of BLV infection. Our data revealed that only furin and the newly discovered PC7 mRNAs are expressed in Raji, B-Jab and LG2 cell lines.

【 授权许可】

Unknown