SummaryAthymic nude mice appear to be an ideal animal model to demonstrate the local Shwartzman reaction; in these mice the reaction can be provoked by both endotoxin and double-stranded RNA.This investigation was supported by grants from the F. G. W. O. (Fonds voor Geneeskundig Wetenschap-pelijk Onderzoek, krediet nr. 3.0048.75) and the Geconcerteerde Onderzoeksacties (Conventie nr. 76/81-IV). The authors are indebted to Dr. M. J. Van Stapel, Dr. C. Peeters and Prof. Dr. V. Desmet for histopathological examination of the skin biopsy specimens.
(S)-9-(2,3-Dihydroxypropyl)adenine, a novel nucleoside analog, the sugar moiety of which is replaced by an aliphatic chain, inhibits the replication in vitro of several DNA and RNA viruses, including vaccinia, herpes simplex (types 1 and 2), measles, and vesicular stomatitis. It is also effective in vivo in reducing the mortality rate of mice inoculated intranasally with vesicular stomatitis virus.
Mice given repeated injections of either synthetic [poly (I)·poly (C)] or natural (mycophage) double-stranded (ds) RNA developed a marked hyporeactivity in their interferon response to these agents. Two different treatment schedules were used to induce hyporeactivity: (a) repeated injections of poly (I)·poly (C) or mycophage ds-RNA on Days 0, 1, 2 and 4 and (b) two injections of either ds-RNA on days 0 and 4. During the hyporesponsive period mice were significantly less protected against intranasal vesicular stomatitis virus (VSV) challenge, but markedly more tolerant to the lethal effects of the double-stranded RNA. However, repeated injections of the mycophage ds-RNA on Days 0, 1, 2 and 4 brought about a significant decrease of interferon production and toxicity, but no loss of protection against VSV challenge. In all other systems, hyporeactivity to interferon production closely paralleled hyporeactivity to antiviral protection and hyporeactivity to toxicity. The findings presented herein tend to reinforce the interpretation that, in welldefined conditions, these three parameters of the biological activity of double-stranded RNA are interrelated.
No abstract is provided for this article.
A three-dimensional common feature pharmacophore model was developed using the X-ray structure of RT/non-nucleoside inhibitor (NNRTI) complexes. Starting from the pharmacophore hypothesis and the structure of the lead compound TBZ, new NNRTIs were designed and synthesized, having the benzimidazol-2-one system as a scaffold. Docking experiments showed that these molecules docked in a position and orientation similar to that of known inhibitors. Biological testing confirmed that our strategy was successful in searching for new leads as NNRTIs.
The HIV genome encodes a small number of viral proteins (i.e., 16), invariably establishing cooperative associations among HIV proteins and between HIV and host proteins, to invade host cells and hijack their internal machineries. As a known example, the HIV envelope glycoprotein GP120 is closely associated with GP41 for viral entry. From a genome-wide perspective, a hypothesis can be worked out to determine whether 16 HIV proteins could develop 120 possible pairwise associations either by physical interactions or by functional associations mediated via HIV or host molecules. Here, we present the first systematic review of experimental evidence on HIV genome-wide protein associations using a large body of publications accumulated over the past 3 decades. Of 120 possible pairwise associations between 16 HIV proteins, at least 34 physical interactions and 17 functional associations have been identified. To achieve efficient viral replication and infection, HIV protein associations play essential roles (e.g., cleavage, inhibition, and activation) during the HIV life cycle. In either a dispensable or an indispensable manner, each HIV protein collaborates with another viral protein to accomplish specific activities that precisely take place at the proper stages of the HIV life cycle. In addition, HIV genome-wide protein associations have an impact on anti-HIV inhibitors due to the extensive cross talk between drug-inhibited proteins and other HIV proteins. Overall, this study presents for the first time a comprehensive overview of HIV genome-wide protein associations, highlighting meticulous collaborations between all viral proteins during the HIV life cycle.
No abstract is provided for this article.
No abstract is provided for this article.
