Bovine immunodeficiency virus (BIV) is a lentivirus of theRetroviridae family which shares morphological, genetic, antigenic, and/or biologic properties with human immunodeficiency virus type 1 (HIV-1) and other animal lentiviruses including equine infectious anemia virus (EIAV) (22,23,68). Although the association of clinical diseases with BIV is still controversial, persistent lymphocytosis, neurological disorders associated with central nervous system lesions, weight loss, diminished milk production, lymphoid hyperplasia, and the presence of opportunistic bacterial infections have been associated with BIV infection (5,47,57,70). Interestingly, studies of rabbits experimentally infected with BIV have shown the development of a disease characterized by a fatal dysfunction of the immune system similar to that observed in humans, nonhuman primates, and cats infected with HIV-1 (or HIV-2), simian immunodeficiency virus, and feline immunodeficiency virus, respectively (34,35).BIV is categorized as a complex nonprimate lentivirus (68). The BIV provirus DNA is 8,960 nucleotides in length with a typical retroviral genomic structure containing the gag, pol, and env genes flanked by long terminal repeats of 589 nucleotides in length at the 5Ј and 3Ј termini (23,68). In proximity to the pol/env junction, the BIV genome also contains additional open reading frames that may encode nonstructural regulatory/ accessory proteins (23,68). These open reading frames are designated vif (viral infectivity factor), tat (trans-activator factor of transcription), rev (regulator of virus expression), vpw, vpy, and tmx. Only the Tat and Rev proteins have been reported to regulate viral expression at the transcriptional and posttranscriptional levels, respectively (21)(22)(23)68). Among the latter proteins, only the Tat protein and its transactivator response element (TAR) located within the long terminal repeat sequence have been intensively studied (3,6,10,19,58,60,72).BIV Rev is a 23-kDa (186-aa-long) phosphoprotein produced from a multiply spliced mRNA that contains the untranslated leader (exon 1) and two encoding exons (exons 2 and 3) (55). It has been shown previously that BIV Rev localizes to the nucleus and nucleoli of BIV-infected cells (56). As reported for HIV-1 Rev, BIV Rev mediates the nuclear exportation of partially spliced viral RNAs encoding structural proteins and of unspliced RNAs that serve as genomic RNA by interacting with a stem-loop structure termed Rev-responsive element (RRE) present in these RNAs (59). The Rev proteins contain at least three central functional domains: a basic arginine-rich domain that mediates RNA binding (RBD) and contains the nuclear/nucleolar localization signal (NLS/NoLS), a multimerization domain, and a leucine-rich domain that is necessary for the nuclear exportation of Rev (51, 59).In HIV-1, the Rev protein shuttles between the nucleus and the cytoplasm of the infected cells via the importin/exportin proteins or nucleoporin pathway (59). The shuttling of HIV-1 Rev into the nucleus is m...

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Archaeal homologs of eukaryotic C/D box small nucleolar RNAs (C/D box sRNAs) guide precise 2′-O-methyl modification of ribosomal and transfer RNAs. Although C/D box sRNA genes constitute one of the largest RNA gene families in archaeal thermophiles, most genomes have incomplete sRNA gene annotation because reliable, fully automated detection methods are not available. We expanded and curated a comprehensive gene set across six species of the crenarchaeal genus Pyrobaculum, particularly rich in C/D box sRNA genes. Using high-throughput small RNA sequencing, specialized computational searches and comparative genomics, we analyzed 526 Pyrobaculum C/D box sRNAs, organizing them into 110 families based on synteny and conservation of guide sequences which determine methylation targets. We examined gene duplications and rearrangements, including one family that has expanded in a pattern similar to retrotransposed repetitive elements in eukaryotes. New training data and inclusion of kink-turn secondary structural features enabled creation of an improved search model. Our analyses provide the most comprehensive, dynamic view of C/D box sRNA evolutionary history within a genus, in terms of modification function, feature plasticity, and gene mobility.

The bovine immunodeficiency virus (BIV) was isolated in 1969 from a cow, R-29, with a wasting syndrome suggesting bovine leucosis. The virus, first designated bovine visna-like virus, remained unstudied until HIV was discovered in 1983. Then, it was demonstrated in 1987 that the bovine R-29 isolate was a lentivirus with striking similarity to the human immunodeficiency virus (HIV). Moreover, BIV has the most complex genomic structure among all identified lentiviruses shown by several regulatory/accessory genes encoding proteins, some of which are involved in the regulation of virus gene expression. This manuscript aims to review biological and molecular aspects of BIV, with emphasis on regulatory/accessory viral genes/proteins which are involved in virus expression.

The Rev protein is essential for the replication of lentiviruses. Rev is a shuttling protein that transports unspliced and partially spliced lentiviral RNAs from the nucleus to the cytoplasm via the nucleopore. To transport these RNAs, the human immunodeficiency virus type 1 (HIV-1) Rev uses the karyopherin β family importin β and CRM1 proteins that interact with the Rev nuclear localization signal (NLS) and nuclear exportation signal (NES), respectively. Recently, we reported the presence of new types of bipartite NLS and nucleolar localization signal (NoLS) in the bovine immunodeficiency virus (BIV) Rev protein. Here we report the characterization of the nuclear import and export pathways of BIV Rev. By using an in vitro nuclear import assay, we showed that BIV Rev is transported into the nucleus by a cytosolic and energy-dependent importin α/β classical pathway. Results from glutathione S -transferase (GST) pulldown assays that showed the binding of BIV Rev with importins α3 and α5 were in agreement with those from the nuclear import assay. We also identified a leptomycin B-sensitive NES in BIV Rev, which indicates that the protein is exported via CRM1 like HIV-1 Rev. Mutagenesis experiments showed that the BIV Rev NES maps between amino acids 109 to 121 of the protein. Remarkably, the BIV Rev NES was found to be of the cyclic AMP (cAMP)-dependent protein kinase inhibitor (PKI) type instead of the HIV-1 Rev type. In summary, our data showed that the nuclear import mechanism of BIV Rev is novel among Rev proteins characterized so far in lentiviruses.