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Chapter 114. Molecular Mechanisms of Microbial Pathogenesis (Part 5)

Numerous virus–target cell interactions have been described, and it is now clear that different viruses can use similar host-cell receptors for entry. The list of certain and likely host receptors for viral pathogens is long. Among the host membrane components that can serve as receptors for viruses are sialic acids, gangliosides, glycosaminoglycans, integrins and other members of the immunoglobulin superfamily, histocompatibility antigens, and regulators and receptors for complement components. A notable example of the effect of host receptors on the pathogenesis of infection comes from comparative binding studies of avian influenza A virus subtype H5N1 and influenza A virus. | Chapter 114. Molecular Mechanisms of Microbial Pathogenesis Part 5 Numerous virus-target cell interactions have been described and it is now clear that different viruses can use similar host-cell receptors for entry. The list of certain and likely host receptors for viral pathogens is long. Among the host membrane components that can serve as receptors for viruses are sialic acids gangliosides glycosaminoglycans integrins and other members of the immunoglobulin superfamily histocompatibility antigens and regulators and receptors for complement components. A notable example of the effect of host receptors on the pathogenesis of infection comes from comparative binding studies of avian influenza A virus subtype H5N1 and influenza A virus strains expressing hemagglutinin subtype H1. The Hl-subtype strains which tend to be highly pathogenic and transmissible from human to human bind to a receptor composed of two sugar molecules sialic acid linked a-2-6 to galactose. This receptor is highly expressed in the airway epithelium. When virus is shed from this surface its transmission via coughing and aerosol droplets is readily facilitated. In contrast H5N1 avian influenza virus binds to sialic acid linked a-2-3 to galactose and this receptor is highly expressed in pneumocytes in the alveoli. Alveolar infection is thought to underlie not only the high mortality rate associated with avian influenza but also the low human-to-human transmissibility rate of this strain which is not readily transported to the airways from which it could be expelled by coughing . Microbial Growth after Entry Once established on a mucosal or skin site pathogenic microbes must replicate before causing full-blown infection and disease. Within cells viral particles release their nucleic acids which may be directly translated into viral proteins positive-strand RNA viruses transcribed from a negative strand of RNA into a complementary mRNA negative-strand RNA viruses or transcribed into a complementary