The HIV-1 Rev binding family of proteins: the dog proteins as a study model.
Various proteins that are required for the building of new complete human immunodeficiency type 1 virions (HIV-1) are coded by unspliced or partly spliced virus-derived mRNAs. HIV-1 has developed special strategies for moving these mRNAs to the cytoplasm to be translated. In the nucleus of the infected cell the virus-derived protein Regulator of expression of viral proteins (Rev) can bind both the viral intron-containing mRNAs and the cellular co-factor HIV-1 Rev binding protein (HRB) and this complex may be shuttled through the nuclear pores. HRB genes have been relatively well conserved during evolution, from Drosophila to humans. However, as a consequence of reading-frame shifts due to nt insertions/deletions, the protein products generated may differ considerably from the prototypal HRB protein, which comprises one Arf-GAP zinc finger domain, several Phenylalanine-Glycine (FG) motifs and four Asparagine-Proline-Phenylalanine (NPF) motifs. This variability is best exemplified by four HRB proteins of the dog, which are discussed here in more detail. The hypothesis is advanced that atypical HRB proteins may not be able to bind Rev and possibly have other, still undetermined, functions. Since the cellular co-factor HRB is essential for viral replication and spread but is not required for cell viability and main bodily functions, it might be an attractive candidate for anti-HIV-1 drug targeting.
Panaro
Maria A
MA
Department of Human Anatomy and Histology, University of Bari, Policlinico - Piazza Giulio Cesare, Bari I-70124, Italy. ma.panaro@anatomia.uniba.it
Mitolo
Vincenzo
V
Cianciulli
Antonia
A
Cavallo
Pasqua
P
Mitolo
Carlo I
CI
Acquafredda
Angela
A
D000595:Amino Acid Sequence; D000818:Animals; D004285:Dogs / Q000378:metabolism*; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
D054321:rev Gene Products, Human Immunodeficiency Virus