Characterization of a full-length infectious clone of bovine foamy virus 3026

The biological features of most foamy viruses(FVs) are poorly understood, including bovine foamy virus(BFV). BFV strain 3026(BFV3026) was isolated from the peripheral blood mononuclear cells of an infected cow in Zhangjiakou, China. A full-length genomic clone of BFV3026 was obtained from BFV3026-infected cells, and it exhibited more than 99% amino acid(AA) homology to another BFV strain isolated in the USA. Upon transfection into fetal canine thymus cells, the full-length BFV3026 clone produced viral structural and auxiliary proteins, typical cytopathic effects, and virus particles. These results demonstrate that the full-length BFV3026 clone is fully infectious and can be used in further BFV3026 research.

Crystal structures of catalytic core domain of BIV integrase: implications for the interaction between integrase and target DNA

Integrase plays a critical role in the recombination of viral DNA into the host genome.Therefore,over the past decade,it has been a hot target of drug design in the fight against type 1 human immunodeficiency virus(HIV-1).Bovine immunodeficiency virus(BIV)integrase has the same function as HIV-1 integrase.We have determined crystal structures of the BIV integrase catalytic core domain(CCD)in two different crystal forms at a resolution of 2.45Åand 2.2Å,respectively.In crystal form I,BIV integrase CCD forms a back-to-back dimer,in which the two active sites are on opposite sides.This has also been seen in many of the CCD structures of HIV-1 integrase that were determined previously.However,in crystal form II,BIV integrase CCD forms a novel face-toface dimer in which the two active sites are close to each other.Strikingly,the distance separating the two active sites is approximately 20Å,a distance that perfectly matches a 5-base pair interval.Based on these data,we propose a model for the interaction of integrase with its target DNA,which is also supported by many published biochemical data.Our results provide important clues for designing new inhibitors against HIV-1.

HIV-1 Vpr protein activates the NF-κB pathway to promote G2/M cell cycle arrest

Viral protein R(Vpr) plays an important role in the replication and pathogenesis of Human immunodeficiency virus type 1(HIV-1). Some of the various functions attributed to Vpr, including the induction of G2/M cell cycle arrest, activating the NF-κB pathway, and promoting viral reverse transcription, might be interrelated. To test this hypothesis, a panel of Vpr mutants were investigated for their ability to induce G2/M arrest and to activate the NF-κB pathway. The results showed that the Vpr mutants that failed to activate NF-κB also lost the activity to induce G2/M arrest, which suggests that inducing G2/M arrest via Vpr depends at least partially on the activation of NF-κB. This latter possibility is supported by data showing that knocking down the key factors in the NF-κB pathway – p65, Rel B, IKKα, or IKKβ– partially rescued the G2/M arrest induced by Vpr.Our results suggest that the NF-κB pathway is probably involved in Vpr-induced G2/M cell cycle arrest.