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 H1-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 α-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 α-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 strand of DNA (retroviruses); for DNA viruses, mRNA may be
transcribed directly from viral DNA, either in the cell nucleus or in the cytoplasm.

acidic and is bathed with fatty acids toxic to many microbes. Skin pathogens such
as staphylococci must tolerate these adverse conditions. Mucosal surfaces are
covered by a barrier composed of a thick mucous layer that entraps microbes and
facilitates their transport out of the body by such processes as mucociliary
clearance, coughing, and urination. Mucous secretions, saliva, and tears contain
antibacterial factors such as lysozyme and antimicrobial peptides as well as
antiviral factors such as interferons. Gastric acidity is inimical to the survival of
many ingested pathogens, and most mucosal surfaces—particularly the
nasopharynx, the vaginal tract, and the gastrointestinal tract—contain a resident
flora of commensal microbes that interfere with the ability of pathogens to
colonize and infect a host.
Pathogens that survive these factors must still contend with host endocytic,
phagocytic, and inflammatory responses as well as with host genetic factors that
determine the degree to which a pathogen can survive and grow. The growth of
viral pathogens entering skin or mucosal epithelial cells can be limited by a variety
of host genetic factors, including production of interferons, modulation of
receptors for viral entry, and age- and hormone-related susceptibility factors; by
nutritional status; and even by personal habits such as smoking and exercise.