Analysis of Jembrana disease virus replication dynamics in vivo reveals strain variation and atypical responses to infection.

Jembrana disease virus (JDV) is an acute lentiviral infection of Bali cattle in Indonesia. Data generated during a series of cattle infection experiments was examined and significant differences were identified in the mean plasma viral load on the first and second days of the febrile response in cattle infected with JDV(TAB/87) compared to those infected with JDV(PUL/01). The peak and total viral loads >or=10(6) genome copies/ml during the acute stage of the disease were significantly higher in JDV(TAB/87) infected cattle. JDV(PUL/01) infected cattle developed peak rectal temperatures earlier than the JDV(TAB/87) cattle but there were no differences in the duration of the febrile responses observed for the 2 groups of animals. The plasma viremia was above 10(6) genome copies/ml for almost 3 days longer in JDV(TAB/87) compared to JDV(PUL/01) infected cattle. Atypical responses to infection occurred in approximately 15% of experimentally infected animals, characterized by reduced viral loads, lower or absent febrile responses and absence of p26-specific antibody responses. Most of these cattle developed normal Tm-specific antibody responses between 4-12 weeks post-infection.

Regulation of microtubule assembly and stability by the transactivator of transcription protein of Jembrana disease virus.

Microtubules are cytoskeletal polymers consisting of tubulin subunits that take part in diverse cell activities. Many viruses hijack cellular motor proteins to move on microtubules toward the cell interior during the entry process and toward the plasma membrane during the egress period. In addition, viruses often remodel microtubules to facilitate the generation of infectious progeny. In this study, we found that the transactivator of transcription protein of Jembrana disease virus (Jtat) bound tubulin and microtubules both in cells and in the purified system. Microtubule co-sedimentation and co-localization assays revealed a robust interaction of Jtat with microtubules. Tubulin turbidity assay further showed that Jtat promoted tubulin polymerization in vitro in a concentration-dependent manner. Moreover, Jtat promoted the partitioning of cellular tubulin toward the polymeric form, increased the level of tubulin acetylation, and significantly enhanced the cold stability of cellular microtubules. In addition, Jtat-mediated disruption of microtubule dynamics induced the release of Bim from microtubules, leading to profound apoptosis. These results not only identify Jtat as an important viral regulator of microtubule dynamics but also indicate that Jtat-induced apoptosis might contribute to Jembrana disease pathogenesis.

Internalization of Jembrana disease virus Tat: possible pathway and implication.

Jembrana disease virus (JDV) is a lentivirus highly related to the bovine immunodeficiency virus (BIV). It causes an acute disease with high mortality rate within 1-2 weeks. JDV encodes the most potent Tat (JTat) of any of the lentiviruses. JTat can transactivate all LTRs and functionally substitute for HIV Tat in the viral genome and may function as a pivotal regulator in the acute pathogenesis of JDV. The goal of this paper is to study JTat internalization by cells, the mechanisms involved in internalization, and the effect of JTat on neighbouring cells. By quantification and fluorescence microscopy, we found that the internalization of extracellular EGFP-JTat fusion protein was both time and dose-dependent, but endocytosis and energy independent. We identified that arginines which were responsible for the internalization. Internalized JTat was distributed in both the nucleus and the cytoplasm, could transactivate JDV LTR and modulate cellular gene expression. Based on our findings, we propose that secretion and internalization of JTat may be a way for JDV to influence neighbouring cells and make the cellular environment more amenable to viral infection.