Principles of Virology, Volume 2. S. Jane Flint

membrane. Beyond this extra cellular matrix are tissue fluids, from which particles may be taken into lymphatic capillaries and reach the blood. Local macrophages patrol the tissue fluids in search of foreign particles. (Right) Viruses that reproduce at different locations within the respiratory tract, noted with the associated clinical syndromes. SARS, severe acute respiratory syndrome; MERS, Middle East respiratory syndrome. Adapted from Mims CA et al. 1995. Mims’ Pathogenesis of Infectious Disease (Academic Press, Orlando, FL).

BOX 2.3

      DISCUSSION

       In praise of mucus

      When you have a cold or sinus infection, it can be disconcerting to take a peek in your tissue after you have blown your nose. However, the thick, colorful mucus that accompanies many such infections actually serves an important purpose. Mucus-producing cells line the mouth, nose, sinuses, throat, lungs, vagina, and entire gastrointestinal tract. In addition to its lubricant function, mucus acts as a protective blanket over these surfaces, preventing the tissue underneath from dehydrating. Mucus also acts as a pathogen flypaper, trapping viruses and bacteria. More than being just a sticky goo, mucus contains antibodies, enzymes that destroy the invaders it traps, and a variety of immune cells poised to respond to pathogens that attach to it.

      It is a common misconception that yellow or green mucus is directly due to the presence of bacteria or viruses. When an individual ac quires a respiratory tract infection, neutrophils, a key element of the host innate response, rush to the infected site. These cells contain an enzyme, myeloperoxidase, that is critical for the ability of neutrophils to eliminate pathogens, as individuals with a genetic loss of this enzyme are immunocompromised, especially for respiratory tract infections. Myeloperoxidase is stored in azurophilic granules prior to release; these granules are naturally green or tan. Thus, when neutrophils are present in large numbers, the mucus appears green. One may indeed assume that discolored mucus is a sign of infection, as recruitment of neutrophils often accompanies infection.

      One final thought that you may wish you did not know: while it is not a very socially acceptable practice, eating one’s own nasal secretions (mucophagy), a habit of many young children, may have some evolutionary benefit. Some have argued that mucophagy pro vides benefits to the immune system, especially the underdeveloped host responses of children. As noted above, mucus destroys most of the pathogens that it tethers, so nasal secretions themselves are unlikely to be laden with infectious virus particles. Rather, introducing these crippled microorganisms into the gut, where antigen-presenting cells are abundant, may be a form of “low-tech” vaccination or immune memory booster.

       Bellows A. 2009. A booger a day keeps the doctor away, p 28–30. In Alien Hand Syndrome and Other Too-Weird-Not-To-Be-True Stories. Workman Publishing, New York, NY.

Many viruses enter the respiratory tract in the form of aerosolized droplets expelled by an infected individual by coughing or sneezing (Fig. 2.8). These include well-known vi ruses such as influenza and rhinoviruses that cause the common cold, but less-known pathogens, including adenoviruses, respiratory syncytial virus, measles, mumps, and hantaviruses, are also transmitted via respiratory droplets. Infection can also spread through contact with respiratory secretions or saliva from an infected individual. Larger, virus-containing droplets are deposited in the nasal mucosa, whereas smaller droplets can penetrate deeper into the airways or the alveoli. To infect the respiratory tract successfully, virus particles must not be captured or swept away by mucus, neutralized by antibody, or destroyed by alveolar macrophages. Attributes of some viruses, such as the neuraminidase protein of influenza virus, facilitate penetration of the thick mucus to enable access to permissive cells below. Influenza neuraminidase cleaves sialic acids that are abundant on the glycoproteins that form mucus; as a result, mucous membranes are degraded locally, affording access to the cells below. Oseltamivir (also known by the brand name Tamiflu), an antiviral that reduces influenza virus symptoms, blocks the function of neuraminidase and thus reduces the risk of infection, but this mechanism also explains why oseltamivir must be taken early after infection to be effective.

How deeply into the respiratory tract a virus penetrates is a direct cause of the kinds of disease that can result, analogous to the correlation of “infection depth” and systemic spread discussed earlier for skin infections. Viruses that reproduce in the upper respiratory tract (nasal passages, throat), such as rhinoviruses, typically tend to cause less severe infections than those that infect the lower respiratory tract, such as influenza virus and the coronavirus that causes severe acute respiratory syndrome (SARS). Moreover, while some viruses, including those noted above, are typically restricted to the respiratory tract, others, such as measles, mumps, rubella, and varicella-zoster virus, use the respiratory tract as a portal to other tissues in the host, causing systemic diseases such as rashes (Box 2.4).

Figure 2.7 Cilia help to move debris trapped in the mucus of the respiratory tract out of the body. Cells residing under the mucus have tiny, hair-like projections called cilia. Usually, the mucus traps incoming particles. In coordinating waves, often referred to as the “mucociliary escalator,” the cilia sweep the mucus either up to the nasal passages or back into the throat, where it is swallowed rather than in haled into the lungs. The acid of the stomach destroys most pathogens not inactivated by the mucus. An influenza virus particle is shown de grading the mucus layer to access the epithelial cells beneath.

Alimentary Tract

      The alimentary tract is another major site of viral invasion and dissemination. Eating, drinking, kissing, and sexual contact routinely place viruses in the gut. Virus particles that infect by the intestinal route must, at a minimum, be resistant to extremes of pH, proteases, and bile detergents. Many enveloped viruses do not initiate infection in the alimentary tract, because viral envelopes are susceptible to dissociation by detergents, such as bile salts.

Figure 2.8 A picture is worth a thousand words. A group of applied mathematicians evaluated the distance and “hang time” of various-sized droplets produced after a sneeze, using the same strategies as ballistics experts studying gunfire. As many as 40,000 droplets can be released in a single sneeze, some traveling over 200 miles an hour. Heavier droplets (seen in the photo) succumb to gravity and fall quickly, while smaller droplets (less than 50μm in diameter) can stay in the air until the droplet dehydrates. Courtesy of CDC/Brian Judd/James Gathany, CDC-PHIL ID#11161.

As depicted in Fig. 2.4, the lumen of the alimentary tract, from mouth to anus, is “outside” of our bodies, and thus the anatomy of the alimentary tube possesses many features of the skin. Like the skin, the gut has physical, chemical, and protein-based barriers that collectively limit viral survival and infection: the stomach is acidic, the intestine is alkaline, and proteases and bile salts are present at high concentrations. In addition, mucus lines the entire tract, and the luminal surfaces of the intestines contain antibodies and phagocytic cells. Moreover, the small and large intestines are coated in a thick (50-μm) paste of symbiotic bacteria that not only aids in digestion and homeostasis but also imposes a formidable physical barrier for virus particles to access the cells beneath. As viruses make their way from mouth to anus, they are confronted