By Dr. F. Brown (auth.), Dr. Margo A. Brinton, Dr. Charles H. Calisher, Dr. Roland Rueckert (eds.)
Positive-strand RNA viruses comprise the vast majority of the plant viruses, a few insect viruses, and animal viruses, reminiscent of coronaviruses, togaviruses, flaviviruses, poliovirus, hepatitis C, and rhinoviruses. Works from greater than 50 best laboratories signify most modern examine on concepts for the regulate of virus ailments: molecular features of pathogenesis and virulence; genome replication and transcription; RNA recombination; RNA-protein interactions and host-virus interactions; protein expression and virion maturation; RNA replication; virus receptors; and virus constitution and meeting. Highlights contain research of the picornavirus IRES point, facts for long-term patience of viral RNA in host cells, acquisition of recent genes from the host and different viruses through copy-choice recombination, id of molecular ambitions and use of structural and molecular organic experiences for improvement of novel antiviral agents.
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Positive-strand RNA viruses comprise nearly all of the plant viruses, a couple of insect viruses, and animal viruses, comparable to coronaviruses, togaviruses, flaviviruses, poliovirus, hepatitis C, and rhinoviruses. Works from greater than 50 best laboratories characterize most up-to-date examine on concepts for the regulate of virus ailments: molecular elements of pathogenesis and virulence; genome replication and transcription; RNA recombination; RNA-protein interactions and host-virus interactions; protein expression and virion maturation; RNA replication; virus receptors; and virus constitution and meeting.
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Neurons of immature (newborn) mice are lysed by SINV infection through induction of apoptosis leading to rapidly fatal disease. Neurons of mature (weanling) mice express genes, such as bcl-2, that render them resistant to induction of apoptosis and these cells become persistently infected by SINV. Virus can be cleared from these persistently infected neurons by treatment with antibody, but one consequence of this mechanism of virus clearance is persistence of viral RNA (Fig. 3). Therefore, longterm downregulation of virus replication requires continued administration of antibody or local production of antibody within the brain, a well-recognized consequence of previous central nervous system infection.
Design of symmetry-based diols Analysis of the crystal structure of the A-74704/HIV PR complex revealed that the short spacing between the PI and PI' NH groups resulted in hydrogen bonds with poor geometry between the inhibitor PI and PI' ami des and the carbonyl groups of Gly27 and Gly127. The replacement of an ethyl alcohol by a glycol isostere has been shown to result in potent renin inhibitors . Thus, a second series of symmetry-based HIV PR inhibitors was designed by application of a C2 axis placed at the midpoint of the scissile bond (Fig.
G. Strauss, California Institute of Technology) recombinant viruses differing only at this position . When these viruses were tested for neurovirulence and replication in mice of different ages, the His substitution was associated with greater mortality in 1 and 2 week-old, but not in 1 day-old mice (Table 2). With His at E2-55 amounts of virus produced within 24h after intracerebral Table 1. Amino acid sequence differences in 3 strains of SINV differing in passage history and neurovirulence for suckling mice (SM) and weanling mice (WM) Strain NSV AR339 HRSP Virulence E2 SM WM 3 23 55 172 209 72 237 313 + + ± + T T I E H A Q R V V Q G G R G E G A A A S D G G El Age-dependent susceptibility to fatal encephalitis 33 Table 2.
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