Analysis of the env gene of a molecularly cloned and biologically active Moloney mink cell focus-forming proviral DNA

Abstract

A biologically active molecular clone of BALB/Moloney mink cell focus-forming (Mo-MCF) proviral DNA has been reconstructed in vitro. It contains the 5'' half of BALB/Moloney murine leukemia virus (Mo-MuLV) DNA and the 3'' half of BALB/Mo-MCF DNA. The complete nucleotide sequence of the env gene and the 3'' long terminal repeat (LTR) of the cloned Mo-MCF DNA was determined and compared with the sequence of the corresponding region of parental Mo-MuLV DNA. The substitution in the Mo-MCF DNA encompasses 1159 base pairs, beginning in the carboxyl terminus of the pol gene and extending to the middle of the env gene. The Mo-MCF env gene product is predicted to be 29 amino acids shorter than the parental Mo-MuLV env gene product. The portion of the env gene encoding the p15E peptide is identical in both viral DNA. There is an additional A residue in the Mo-MCF viral DNA in a region just preceding the 3'' LTR. The nucleotide sequence of the 3'' LTR of Mo-MCF DNA is similar to that of the 5'' LTR of BALB/Mo-MuLV DNA with the exception of 2 single base substitutions. Evidently, the sequence substitution in the env gene is responsible for the dual-tropic properties of Mo-MCF viruses.