Molecular epidemiology of infectious bursal disease virus in Zambia

Nucleotide sequences of the VP2 hypervariable region (VP2-HVR) of 10 infectious bursal disease viruses detected in indigenous and exotic chickens in Zambia from 2004 to 2005 were determined. Phylogenetic analysis showed that the viruses diverged into two genotypes and belonged to the African very virulent types (VV1 and VV2). In the phylogenetic tree, strains in one genotype clustered in a distinct group and were closely related to some strains isolated in western Africa (VV1), with nucleotide similarities of 95.7%– 96.5%. Strains in the other genotype were clustered within the eastern African VV type (VV2), with nucleotide similarities of 97.3%– 98.5%. Both genotypes were distributed in the southern parts of Zambia and had a unique conserved amino acid substitution at 300 (E→A) in addition to the putative virulence marker at positions 222(A), 242(I), 256(I), 294(I) and 299(S). These findings represent the first documentation of the existence of the African VV-IBDV variants in both indigenous and exotic chickens in Zambia

Herbig Ae/Be Stars in the Magellanic Bridge

We have found Herbig Ae/Be star candidates in the western region of the Magellanic Bridge. Using the near infrared camera SIRIUS and the 1.4 m telescope IRSF, we surveyed about 3.0 deg x 1.3 deg (24 deg < RA < 36 deg, -75 deg < Dec. < -73.7 deg) in the J, H, and Ks bands. On the basis of colors and magnitudes, about 200 Herbig Ae/Be star candidates are selected. Considering the contaminations by miscellaneous sources such as foreground stars and early-type dwarfs in the Magellanic Bridge, we estimate that about 80 (about 40%) of the candidates are likely to be Herbig Ae/Be stars. We also found one concentration of the candidates at the young star cluster NGC 796, strongly suggesting the existence of pre-main-sequence (PMS) stars in the Magellanic Bridge. This is the first detection of PMS star candidates in the Magellanic Bridge, and if they are genuine PMS stars, this could be direct evidence of recent star formation. However, the estimate of the number of Herbig Ae/Be stars depends on the fraction of classical Be stars, and thus a more precise determination of the Be star fraction or observations to differentiate between the Herbig Ae/Be stars and classical Be stars are required.Comment: 22 pages, 6 figures. Accepted for publication in Ap

HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation.

The internal ribosome entry site (IRES) of the hepatitis C virus (HCV) drives noncanonical initiation of protein synthesis necessary for viral replication. Functional studies of the HCV IRES have focused on 80S ribosome formation but have not explored its role after the 80S ribosome is poised at the start codon. Here, we report that mutations of an IRES domain that docks in the 40S subunit's decoding groove cause only a local perturbation in IRES structure and result in conformational changes in the IRES-rabbit 40S subunit complex. Functionally, the mutations decrease IRES activity by inhibiting the first ribosomal translocation event, and modeling results suggest that this effect occurs through an interaction with a single ribosomal protein. The ability of the HCV IRES to manipulate the ribosome provides insight into how the ribosome's structure and function can be altered by bound RNAs, including those derived from cellular invaders

Interplay between NS3 protease and human La protein regulates translation-replication switch of Hepatitis C virus

HCV NS3 protein plays a central role in viral polyprotein processing and RNA replication. We demonstrate that the NS3 protease (NS3pro) domain alone can specifically bind to HCV-IRES RNA, predominantly in the SLIV region. The cleavage activity of the NS3 protease domain is reduced upon HCV-RNA binding. More importantly, NS3pro binding to the SLIV hinders the interaction of La protein, a cellular IRES-trans acting factor required for HCV IRES-mediated translation, resulting in inhibition of HCV-IRES activity. Although overexpression of both NS3pro as well as the full length NS3 protein decreased the level of HCV IRES mediated translation, replication of HCV replicon RNA was enhanced significantly. These observations suggest that the NS3pro binding to HCV IRES reduces translation in favor of RNA replication. The competition between the host factor (La) and the viral protein (NS3) for binding to HCV IRES might regulate the molecular switch from translation to replication of HCV

Ablation of NG2 Proteoglycan Leads to Deficits in Brown Fat Function and to Adult Onset Obesity

Obesity is a major health problem worldwide. We are studying the causes and effects of obesity in C57Bl/6 mice following genetic ablation of NG2, a chondroitin sulfate proteoglycan widely expressed in progenitor cells and also in adipocytes. Although global NG2 ablation delays early postnatal adipogenesis in mouse skin, adult NG2 null mice are paradoxically heavier than wild-type mice, exhibiting larger white fat deposits. This adult onset obesity is not due to NG2-dependent effects on CNS function, since specific ablation of NG2 in oligodendrocyte progenitors yields the opposite phenotype; i.e. abnormally lean mice. Metabolic analysis reveals that, while activity and food intake are unchanged in global NG2 null mice, O2 consumption and CO2 production are decreased, suggesting a decrease in energy expenditure. Since brown fat plays important roles in regulating energy expenditure, we have investigated brown fat function via cold challenge and high fat diet feeding, both of which induce the adaptive thermogenesis that normally occurs in brown fat. In both tests, body temperatures in NG2 null mice are reduced compared to wild-type mice, indicating a deficit in brown fat function in the absence of NG2. In addition, adipogenesis in NG2 null brown pre-adipocytes is dramatically impaired compared to wild-type counterparts. Moreover, mRNA levels for PR domain containing 16 (PRDM16) and peroxisome proliferator-activated receptor γ coactivator (PGC)1-α, proteins important for brown adipocyte differentiation, are decreased in NG2 null brown fat deposits in vivo and NG2 null brown pre-adipocytes in vitro. Altogether, these results indicate that brown fat dysfunction in NG2 null mice results from deficits in the recruitment and/or development of brown pre-adipocytes. As a consequence, obesity in NG2 null mice may occur due to disruptions in brown fat-dependent energy homeostasis, with resulting effects on lipid storage in white adipocytes

Very early multi-color observations of the plateau phase of GRB 041006 afterglow

Observations of the optical afterglow of GRB 041006 with the Kiso Observatory 1.05 m Schmidt telescope, the Lulin Observatory 1.0 m telescope and the Xinglong Observatory 0.6 m telescope. Three-bands (B, V and R) of photometric data points were obtained on 2004 October 6, 0.025-0.329 days after the burst. These very early multi band light curves imply the existence of a color dependent plateau phase. The B-band light curve shows a clear plateau at around 0.03 days after the burst. The R band light curve shows the hint of a plateau, or a possible slope change, at around 0.1 days after the burst. The overall behavior of these multi-band light curves may be interpreted in terms of the sum of two separate components, one showing a monotonic decay the other exhibiting a rising and a falling phase, as described by the standard afterglow model.Comment: 11 pages, 2 figures, Accepted to ApJ Letter

SARS-CoV-2 ORF3b is a potent interferon antagonist whose activity is increased by a naturally occurring elongation variant

One of the features distinguishing SARS-CoV-2 from its more pathogenic counterpart SARS-CoV is the presence of premature stop codons in its ORF3b gene. Here, we show that SARS-CoV-2 ORF3b is a potent interferon antagonist, suppressing the induction of type I interferon more efficiently than its SARS-CoV ortholog. Phylogenetic analyses and functional assays reveal that SARS-CoV-2-related viruses from bats and pangolins also encode truncated ORF3b gene products with strong anti-interferon activity. Furthermore, analyses of approximately 17,000 SARS-CoV-2 sequences identify a natural variant in which a longer ORF3b reading frame was reconstituted. This variant was isolated from two patients with severe disease and further increased the ability of ORF3b to suppress interferon induction. Thus, our findings not only help to explain the poor interferon response in COVID-19 patients but also describe the emergence of natural SARS-CoV-2 quasispecies with an extended ORF3b gene that may potentially affect COVID-19 pathogenesis