Search

Little is known about the relationship of Gammaherpesviruses with their bat hosts. Gammaherpesviruses are of interest because of their long-term infection of lymphoid cells and their potential to cause cancer. Here, we report the characterization of a novel bat herpesvirus isolated from a big brown bat (Eptesicus fuscus) in Canada. The genome of the virus, tentatively named Eptesicus fuscus herpesvirus (EfHV), is 166,748 base pairs. Phylogenetically EfHV is a member of Gammaherpesvirinae, in which it belongs to the Genus Rhadinovirus and is closely related to other bat Gammaherpesviruses. In contrast to other known Gammaherpesviruses, the EfHV genome contains coding sequences similar to those of class I and II host major histocompatibility antigens. The virus is capable of infecting and replicating in human, monkey, cat and pig cell lines. Although we detected EfHV in 20 of 28 big brown bats tested, these bats lacked neutralizing antibodies against the virus., (Copyright © 2018 Elsevier Inc. All rights reserved.)

APOBEC3G (A3G) is a cytidine deaminase that restricts HIV-1 replication by inducing G-to-A hypermutation in viral DNA; deamination-independent mechanisms are also implicated. HIV-1 Vif protein counteracts A3G by inducing its proteasomal degradation. Thus, the Vif-A3G axis is a potential therapeutic target. To identify compounds that inhibit Vif:A3G interaction, a 307,520 compound library was tested in a TR-FRET screen. Two identified compounds, redoxal and lomofungin, inhibited HIV-1 replication in peripheral blood mononuclear cells. Lomofungin activity was linked to A3G, but not pursued further due to cytotoxicity. Redoxal displayed A3G-dependent restriction, inhibiting viral replication by stabilizing A3G protein levels and increasing A3G in virions. A3G-independent activity was also detected. Treatment with uridine or orotate, intermediates of pyrimidine synthesis, diminished redoxal-induced stabilization of A3G and antiviral activity. These results identify redoxal as an inhibitor of HIV-1 replication and suggest its ability to inhibit pyrimidine biosynthesis suppresses viral replication by augmenting A3G antiviral activity., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The 130-kDa bovine herpesvirus-1 (BHV-1) glycoprotein GVP 6 was found to cross-react immunologically with the herpes simplex glycoprotein gB. Antibodies in polyclonal serum against gB immunoprecipitated GVP 6 and its cleavage products from a lysate of BHV-1-infected cells. Conversely, polyclonal serum against GVP 6 precipitated gB from HSV-1-infected cell lysates. Sera against the other glycoproteins did not demonstrate cross-reactivity. A 3.6-kb Kpnl-Hpal fragment of BHV-1 DNA that hybridized to the gene for gB was cloned and the nucleotide sequence of both strands was determined. The longest codon reading frame in the fragment coded for a protein that showed extensive homology with gB1 and related sequences from pseudorabies virus, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus. The strongest homologies were observed in two segments of the ectodomain, the transmembrane domain, and sequences adjacent to the transmembrane domain.

Hybridoma cell lines producing monoclonal antibodies to bovine herpes virus type 1 (BHV-1) were established. The monoclonal antibodies were characterized with respect to their antigen specificities and biological activities. One group of eight monoclonal antibodies precipitated the glycoproteins GVP 3 (180K) and GVP 9 (91K), a second group of thirteen monoclonal antibodies precipitated GVP 6 (130K), GVP 11 (74K) and GVP 16 (55K), and one monoclone secreted antibodies specific for GVP 7 (105K). Analysis of the immune precipitates by electrophoresis under nonreducing conditions suggested that GVP 3 is a dimer of GVP 9. It also indicated that GVP 11 and GVP 16 are components of a disulfide-linked complex, GVP 6. The results, obtained by immunoprecipitation were confirmed by Western blot analysis and an enzyme-linked immunosorbent assay (ELISA), using electrophoretically separated viral glycoproteins. In addition, these techniques demonstrated differential reactivities of the monoclonal antibodies with GVP 11 and GVP 16. The monoclonal antibodies were used to analyze the biological roles of these three sets of glycoproteins. Monoclonal antibodies directed against GVP 3/GVP 9 did not neutralize viral infectivity, but most of them mediated complement-dependent lysis of the infected cell. Individual monoclonal antibodies directed against GVP 6/GVP 11/GVP 16 could neutralize virus as well as participate in complement-mediated lysis. The only available monoclone against GVP 7 did not show any biological activity in the above two assays. Thus, GVP 6/GVP 11/GVP 16 may contain the attachment site of the virion.