Function of the human immunodeficiency virus types 1 and 2 Rev proteins is dependent on their ability to interact with a structured region present in env gene mRNA.
The interaction of the human immunodeficiency virus type 1 (HIV-1) Rev protein with a structured region in env mRNA (the Rev-responsive element [RRE]) mediates the export of structural mRNAs from the nucleus to the cytoplasm. We demonstrated that unlike HIV-1 Rev, which functions with both the HIV-1 and HIV-2 RREs, HIV-2 Rev functions only with the HIV-2 RRE. Rev-RRE binding studies suggested that the lack of nonreciprocal complementation stems from the inability of HIV-2 Rev to interact with HIV-1 RRE RNA. Maintenance of RNA secondary structure, rather than the primary nucleotide sequence, appeared to be the major determinant for interaction of both HIV-1 and HIV-2 Rev with the HIV-2 RRE. Moreover, the binding domain of the HIV-2 RRE recognized by HIV-1 Rev was dissimilar to the binding domain of the HIV-1 RRE, in terms of both secondary structure and primary nucleotide sequence. Our results support the hypothesis that function of HIV Rev proteins and possibly the functionally similar Rex proteins encoded by the human T-cell leukemia viruses (HTLVs) HTLV-I and HTLV-II is controlled by the presence of RNA secondary structure generated within the RRE RNA.
Department of Molecular Oncology and Virology, Roche Research Center, Nutley, New Jersey 07110-1199.
P J
PJ
Dillon
P
P
Nelbock
A
A
Perkins
C A
CA
Rosen
D001483:Base Sequence; D001665:Binding Sites; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics; D015694:Gene Products, rev / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D005814:Genes, Viral; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics*; D015498:HIV-2 / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D015183:Restriction Mapping; D015302:Simian Immunodeficiency Virus / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000235:genetics*; D054321:rev Gene Products, Human Immunodeficiency Virus
D015694:Gene Products, rev; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015534:Trans-Activators; D014759:Viral Envelope Proteins; D054321:rev Gene Products, Human Immunodeficiency Virus