PERIPHERAL-BLOOD MONONUCLEAR-CELLS FROM SHEEP INFECTED WITH A VARIANTOF BOVINE LEUKEMIA-VIRUS SYNTHESIZE ENVELOPE GLYCOPROTEINS BUT FAIL TO INDUCE SYNCYTIA IN CULTURE

Peripheral blood mononuclear cells (PBMCs) infected with the oncogenic retrovirus bovine leukemia virus (BLV) produce virus when cultured br iefly. BLV can be transmitted in cocultures to adherent susceptible ce lls, which become infected, express viral proteins, and fuse into mult inucleated syncytia several days later. PBMCs from 3 of 10 BLV-infecte d sheep displayed a lifelong deficiency in induction of syncytium form ation among indicator cells in culture, although large numbers of PBMC s synthesized viral transcripts or capsid protein. Since the infected, syncytium-deficient PBMCs were greater than or equal to 97% B cells, the deficiency could not be attributed to altered host cell tropism. T he syncytium-deficient phenotype was recapitulated in newly infected s heep, demonstrating that this property is regulated by the viral genot ype. The alteration in the BLV genome delayed but aid not prohibit the establishment of BLV infection in vivo. Envelope glycoproteins were s ynthesized in syncytium-deficient PBMCs, translocated to the cell surf ace, and incorporated into virions. However, monoclonal antibodies spe cific for the BLV surface glycoprotein did not stain fixed PBMCs of th e syncytium-deficient phenotype. Moreover, an animal with syncytium-de ficient PBMCs had lower titers of neutralizing antibodies throughout t he first 5 years of infection than an animal with similar numbers of i nfected PBMCs of the syncytium-inducing phenotype. The syncytium-defic ient variant productively infected indicator cells at greatly reduced efficiency, shelling that the alteration affects an early step in vira l entry or replication. These results suggest that the alteration maps in the env gene or in a gene whose product affects the maturation or conformation, and consequently the function, of the envelope protein c omplex.