Mutational Analysis of the Bovine Hepacivirus Internal Ribosome Entry Site.

In recent years, hepatitis C virus (HCV)-related viruses were identified in several species, including dogs, horses, bats, and rodents. In addition, a novel virus of the genus Hepacivirus has been discovered in bovine samples and was termed bovine hepacivirus (BovHepV). Prediction of the BovHepV internal ribosome entry site (IRES) structure revealed strong similarities to the HCV IRES structure comprising domains II, IIIabcde, pseudoknot IIIf, and IV with the initiation codon AUG. Unlike HCV, only one microRNA-122 (miR-122) binding site could be identified in the BovHepV 5' nontranslated region. In this study, we analyzed the necessity of BovHepV IRES domains to initiate translation and investigated possible interactions between the IRES and core coding sequences by using a dual luciferase reporter assay. Our results suggest that such long-range interactions within the viral genome can affect IRES-driven translation. Moreover, the significance of a possible miR-122 binding to the BovHepV IRES was investigated. When analyzing translation in human Huh-7 cells with large amounts of endogenous miR-122, introduction of point mutations to the miR-122 binding site resulted in reduced translation efficiency. Similar results were observed in HeLa cells after substitution of miR-122. Nevertheless, the absence of pronounced effects in a bovine hepatocyte cell line expressing hardly any miR-122 as well suggests additional functions of this host factor in virus replication.IMPORTANCE Several members of the family Flaviviridae, including HCV, have adapted cap-independent translation strategies to overcome canonical eukaryotic translation pathways and use cis-acting RNA-elements, designated viral internal ribosome entry sites (IRES), to initiate translation. Although novel hepaciviruses have been identified in different animal species, only limited information is available on their biology on molecular level. Therefore, our aim was a fundamental analysis of BovHepV IRES functions. The findings which show that functional IRES elements are also crucial for BovHepV translation expand our knowledge on molecular mechanism of hepacivirus propagation. We also studied the possible effects of one major host factor implicated in HCV pathogenesis, miR-122. The results of mutational analyses suggested that miR-122 enhances virus translation mediated by BovHepV IRES.

Osteolytic lesions and bacillary angiomatosis in HIV infection: radiologic differentiation from AIDS-related Kaposi sarcoma.

Bacillary angiomatosis is a newly recognized multisystem bacterial infectious disease seen in the setting of human immunodeficiency virus (HIV) infection. The disease is marked by cutaneous vascular lesions that contain a bacterium similar to the cat scratch disease bacillus. Antibiotic therapy leads to the resolution of both cutaneous and systemic manifestations. Of 17 HIV-infected patients with cutaneous lesions of bacillary angiomatosis, six (35%) had symptomatic osteolytic bone lesions that improved following antibiotic therapy. The authors describe the appearance of the bone lesions on radiographs, computed tomographic (CT) scans, magnetic resonance (MR) images, and radionuclide studies. Osteolytic lesions are a relatively common feature of bacillary angiomatosis in patients with HIV infection. The presence of bone lesions aids in differentiation of bacillary angiomatosis from acquired immunodeficiency syndrome-related Kaposi sarcoma, which has similar cutaneous abnormalities but no associated bone lesions.