By R. M. Zinkernagel (auth.), Professor Dr. Michael B. A. Oldstone (eds.)
Viruses are studied both simply because they reason major human, animal or plant ailment or simply because they're invaluable fabrics for probing easy phenomena in biology, chemistry, genetics and/or molecular biology. Arenaviruses are surprisingly fascinating in that they occupy either different types. Arenaviruses reason numerous human illnesses identified essentially because the hemorrhagic fevers happening in South and Latin the United States (Bolivia: Machupo, Argentine, Junin virus, and Brazil: Sabia virus) and in Africa (Lassa fever virus). simply because such viruses produce profound disabilities and infrequently kill the folks they infect, they're a resource of well-being challenge and financial worry within the international locations the place they're normal. additional, they supply new difficulties for healthcare individuals as a result of the narrowing of the area as viewers from many nations commute more and more to and from endemic components and will incubate the infectious agent taking it from a pandemic zone into a space the place the virus isn't anticipated. Such instances at the moment are being re corded with expanding frequency. as well as those hemor rhagic fever viruses, the arenavirus lymphocytic choriomeningitis virus (LCMV) can infect people all over the world, even if the disorder is commonly much less disabling and serious than these elicited via the opposite arenaviruses. but, LCMV is of better main issue to non arenavirologists and experimentalists utilizing tissue tradition or ani mals, and so forth. , simply because normal-appearing cultured cells or tissues from animals used for examine can be many times contaminated with LCMV with out manifesting medical sickness or cytopathology and should transmit that an infection to laboratory workers.
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Additional resources for Arenaviruses II: The Molecular Pathogenesis of Arenavirus Infections
There is accumulating evidence, however, that STAT I also can serve as an inhibitor of gene expression. The IFN-C(/~ cytokines normally inhibit cellular proliferation in vitro in part by inhibiting the expression of certain genes such as the cellular proto-oncogene c-myc. In the absence of ST ATI, the inhibitory effects are abrogated (RAMANA et al. 2000). Thus, the picture emerging is that ST A Tl can have both positive and negative effects on gene transcription. Hence, IFN-C(/~-mediated signal tranduction for biological effects can be mediated through STA Tl, either positively or negatively, can be independent of STAT I, or is the net combinatorial result of these pathways.
Changes in lytic function can also be observed in the different compartments during LCMV infections. Two days after infection, cytolytic activity against NK sensitive Y AC-l target cells is enhanced by more than twofold in peripheral blood populations, fivefold in the spleen, and nearly tenfold in the liver (Fig. 5). These activities are also abrogated upon depletion with anti-AGMI. "",J 2% Liver N K 1 . 1 - - - - - - - - - - - - - - - - - -•• Fig. 4A,B. Compartmental distributions of NK cells during LCMV infection.
The decreased NK cell cytotoxicity in STATI-deficient mice is consistent with the observation that the perforin gene promoter contains ST ATI binding sites (Yu et al. 1999). In contrast, ST A Tl does not appear to be required for the induction of NK cell blastogenesis during LCMV infection, as NK cell blastogenesis is induced to similar extents in STAT I-deficient mice compared to their immunocompetent counterparts (Fig. 9B). Thus, during LCMV infections, STATI is required for induction of NK cell cytotoxicity but is dispensable for blastogenesis.
Arenaviruses II: The Molecular Pathogenesis of Arenavirus Infections by R. M. Zinkernagel (auth.), Professor Dr. Michael B. A. Oldstone (eds.)