ABNORMAL PROCESSING OF A RECOMBINANT FELINE LEUKEMIA-VIRUS ENVELOPE POLYPROTEIN AND ITS INTERFERENCE WITH SUBGROUP-C VIRUS-INFECTION

Processing of the env polyprotein of a noninfectious feline leukemia v irus (FeLV) recombinant, named r6gp, was examined in human-transfected cells. The r6gp provirus was previously generated in the frame of FeL V, subgroup a, GA clone with substitution of all but 40 C-terminal ami no acid sequences of the surface glycoprotein (SU) from an endogenous FeLV provirus element (CFE-6). Although r6gp produced a normal size (8 5 kDa) env glycoprotein precursor, the product, unlike the precursor o f the parental virus, was neither additionally glycosylated nor furthe r processed into mature env proteins. Biochemical observations were co nsistent with the idea that the chimeric env polyprotein was trapped i n the endoplasmic reticulum (ER) and were directly supported by immuno fluorescence microscopy analyses. Interestingly, the residence of the chimeric protein in the ER specifically interfered with FeLV, subgroup C (Sarma) virus infection but not the parental FeLV-B virus infection . Since FeLV-C provirus sequences could be readily detected in the inf ected cells, it appeared that r6gp env expression did not block entry of the challenge virus. While FeLV-B and CFE-6 env genes share an exte nsive overall sequence homology, a variable region (region VI) of CFE- 6 near the C-terminus of SU, which was retained in the r6gp construct, exhibits a considerably higher degree of homology to FeLV-C than FeLV -B. Thus, we propose that region VI is involved in conferring specific ity for the env polyprotein oligomerization in the ER, and that co-oli gomerization of the trapped r6gp env with FeLV-C is the reason for spe cific interference with FeLV-C infection. The results also demonstrate for the first time a functional abnormality of a recombinant FeLV env gene which is structurally similar to those commonly detected in FeLV -induced feline lymphosarcomas. (C) 1994 Academic Press, Inc.