In order to map pathogenic determinants, chimeric viruses were prepared between FIV-C36 and FIV-PPR, with reciprocal exchanges involving (i) the 3′ halves of the viruses, including the Vif, OKA, and Env genes; (ii) the 5′ end extending from the 5′ long terminal repeat (LTR) to the beginning of the capsid (CA)-coding region; and (iii) the 3′ LTR and Rev2-coding regions. Ex vivo replication rates and in vivo replication and pathologies were then assessed and compared to those of the parental viruses. The results show that FIV-C36 replicates ex vivo and in vivo to levels approximately 20-fold greater than those of FIV-PPR. None of the chimeric FIVs recapitulated

the replication rate of FIV-06, although most replicated to levels similar to those of FIV-PPR. The rates of chloramphenicol acetyltransferase learn more gene transcription driven by the FIV-C36 and FIV-PPR LTRs were identical. Furthermore, the GDC-0973 in vivo ratios of surface glycoprotein (SU) to capsid protein (CA) in the released particles were essentially the same in

the wild-type and chimeric FIVs. Tests were performed in vivo on the wild-type FfVs and chimeras carrying the 3′ half of FIV-C36 or the 3′ LTR and Rev2 regions of FIV-C36 on the PPR background. Both chimeras were infectious in vivo, although replication levels were lower than for the parental viruses. The chimera carrying the 3′ half of FIV-C36 demonstrated an intermediate disease course with a delayed peak viral load but ultimately resulted in significant reductions in neutrophil and CD4(+) T cells, suggesting potential adaptation in vivo. Taken together, the findings suggest that the rapid-growth phenotype and pathogenicity of FIV-C36 are the result of evolutionary fine tuning throughout the viral genome, rather than being properties of any one constituent.”
“Psychostimulant use increases anxious behavior, likely through interactions between central corticotropin-releasing factor (CRF) and serotonergic systems. The current study examined whether chronic amphetamine treatment (2.5 mg/kg, 14 days) or withdrawal

altered CRF receptor densities in the serotonergic dorsal raphe nucleus (dRN). Amphetamine treatment increased CRF2 receptor densities in most subregions no of the dRN, and CRF2 receptors were still elevated following 6 weeks of withdrawal. No changes in CRF1 receptor densities were observed following amphetamine treatment or during withdrawal. Selective increases in dRN CRF, receptors may be related to increased anxiety-like behaviors following psychostimulant use. (C) 2008 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.”
“Nonstructurall protein 5A (NS5A) of the hepatitis C virus (HCV) possesses multiple and diverse functions in RNA replication, interferon resistance, and viral pathogenesis. Recent studies suggest that NS5A is involved in the assembly and maturation of infectious viral particles; however, precisely how NS5A participates in virus production has not been fully elucidated.