Identification of the caprine arthritis encephalitis virus Rev protein and its cis-acting Rev-responsive element.
Caprine Arthritis Encephalitis Virus (CAEV) is a lentivirus closely related to visna virus of sheep and more distantly related to the human lentivirus HIV-1. The genomes of lentiviruses contain additional genes that regulate the lentivirus gene expression; one of these is Rev, a protein that regulates the expression of viral proteins via post-transcriptional mechanisms. A cDNA clone was isolated from CAEV infected cells and shown to encode the 18-kDa Rev protein of CAEV. Antibodies against CAEV Rev (Rev-C) demonstrated that the CAEV Rev protein accumulated in the nucleus and in particular in the nucleolus of transiently transfected cells. Mutation of a basic region in the CAEV Rev protein resulted in loss of nucleolar localization. A highly structured RNA element has been identified in the env gene of CAEV (nt 7850-8150); its structure and location suggested that it was analogous to the Rev-responsive element (RRE) of HIV-1 and visna virus. A 300-bp fragment (nt 7850-8150) spanning this region was substituted for the HIV-1 RRE in an HIV-1 Gag expression vector. Expression of the Gag protein was dramatically increased when Rev-C was added in trans, indicating that this fragment contained the cis-acting CAEV Rev Responsive Element. Cross-activation by the Rev/Rex proteins of other lentiviruses and members of the HTLV-I family indicated that this RRE could interact with Rev or Rex proteins of other viruses. This suggests that the highly divergent lentiviruses share similar mechanisms and cofactors regulating post-transcriptional viral gene expression. The Rev/RRE mechanism is thus the most conserved regulatory mechanism in lentiviruses and other complex retroviruses.
Saltarelli
M J
MJ
Frederick Cancer Research and Development Center, Human Retrovirus Section, Maryland 21702.
Schoborg
R
R
Pavlakis
G N
GN
Clements
J E
JE
D000595:Amino Acid Sequence; D000818:Animals; D016088:Arthritis-Encephalitis Virus, Caprine / Q000235:genetics*; D003001:Cloning, Molecular; D004279:DNA, Viral; D005455:Fluorescent Antibody Technique; D015694:Gene Products, rev / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D012045:Regulatory Sequences, Nucleic Acid
D004279:DNA, Viral; D015694:Gene Products, rev