The inhibitory activity of several fluoroquinolone antibiotics against human immunodeficiency virus type 1 (HIV-1) replication was investigated. R-71762, (±) 9-fluoro-3-fluoromethyl-2,3-dihydro-10-[4-(2-pyridyl)-1-piperazinyl]-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid, protected MT-4 cells from HIV-1-induced cytopathic effects. Furthermore, the compound inhibited virus replication both in acutely and in chronically HIV-1-infected cells. On the other hand, ofloxacin, levofloxacin, ciprofloxacin, norfloxacin and enoxacin, that were previously reported to be protective against HIV-1-induced cytopathic effects, did not show any protective activity in our assay system. These results indicate that R-71762 is a novel inhibitor of HIV-1 replication and is effective even in HIV-1 chronically infected cells.
Studies on Marek's disease virus serotype 2 (MDV2) are important for understanding the natural nonpathogenic phenotypes of MDV. We determined the 16 770 bp nucleotide sequence of the MDV2 genome located in the right part the of unique long region. The analysis revealed 12 complete open reading frames (ORFs) with high amino acid sequence identities to the gene products of other alphaherpesviruses. The MDV2 ORFs were arranged collinearly with the prototype sequence of herpes simplex virus type 1 ranging from the UL41 to UL51 genes. Except for the MDV2 UL41 gene, all of the identified genes were confirmed to be transcribed with 3h-coterminal mRNAs and/or a unique transcript in the virus-infected cells. Transcriptional patterns for the regions of the MDV2 UL48 to UL49.5 genes were notably different from the similar area of MDV serotype 1.Marek's disease virus (MDV) is the causative agent of a contagious malignant T-cell lymphoma in chickens. It is divided into three serotypes : MDV serotype 1 (MDV1) includes oncogenic strains and their attenuated strains ; MDV3 (herpesvirus of turkeys ; HVT) includes nonpathogenic strains and has been used for one of the effective vaccines against Marek's disease (MD) ; MDV2 includes the naturally nonpathogenic strains isolated from chickens and other birds belonging to the genus Gallus (Lin et al., 1990). Several strains of MDV2 and the attenuated MDV1 have also been used as effective vaccines, mainly in combination with HVT vaccines (Witter, 1992).
The role of the integrase region of feline immunodeficiency virus (FIV) in viral replication was examined using an integrase mutant clone of FIV which carries a frameshift mutation in the region. Upon transfection, although the integrase mutant was able to release virus-like particles into the supernatant from the transfected cells, the virions produced by the mutant contained unprocessed gag precursor protein and undetectable levels of reverse transcriptase activity. Furthermore, the mutant virions were unable to direct the synthesis of viral DNA after infection in target cells. To understand this phenotype of the integrase mutant in more detail, we constructed a gag-pol expression plasmid from an FIV molecular clone and assayed roles of the integrase region on virus particle formation following transfection. When an inframe deletion was introduced into the protease region of the expression plasmid, the mutant was able to efficiently release gag- and gag-pol precursor proteins into the supernatant from the transfected cells. An expression plasmid with mutations in both the protease and integrase regions, however, failed to release the gag-pol precursor protein from the cells. These results suggested an essential role for the integrase region for efficient incorporation of the gag-pol precursor into the virions.
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