Читать книгу Principles of Virology, Volume 2 - Jane Flint, S. Jane Flint - Страница 67

The skin is the largest organ of the body, weighing more than 9 kg (20 pounds) in an average adult. It serves obvious protective functions, but is also required for thermoregulation, control of hydration and evaporation, and integration of sensory information. The external surface of the skin, or epidermis, is composed of several layers, including a basal germinal layer of proliferating cells, a granular layer of dying cells, and an outer layer of dead, keratinized cells (Fig. 2.5). This outermost layer is a rather literal coat of armor against viral infection: many virus particles that land on intact skin are inactivated by dehydration, acids, or other inhibitors secreted by commensal microorganisms. Some virus particles are removed from the body when dead cells slough of; many others are washed away by soap and water. However, when the integrity of the dead cell layer is compromised by cuts, abrasions, or punctures (e.g., insect bites and needle sticks), virus particles can access the rich array of live cells beneath the keratinized layer, including epithelial cells, endothelial cells, neuronal processes, and capillaries.

Examples of viruses that can gain entry via the skin include some human papillomaviruses, certain poxviruses (e.g., myxoma virus), and all tick- or mosquito-borne viruses that are transmitted by arthropod injection below the dead cell layer. Even deeper inoculation into the tissue below the dermis can occur by hypodermic needle punctures, body piercing, tattooing, or sexual contact when body fluids are mingled as a result of skin abrasions or ulcerations. Viruses that can gain entry in this manner include hepatitis B and C, human immunodeficiency virus type 1, and the herpesviruses Epstein-Barr virus and cytomegalovirus. Finally, rabies virus can be transmitted by animal bites that penetrate deep into tissue and muscle that are rich with nerve endings. Access to nerve terminals provides an opportunity for infection of motor neurons that ultimately leads to the nerve damage often associated with rabies virus infection. Superficial infections in the epidermis typically remain focalized (e.g., papillomaviruses that cause warts), whereas deeper penetration of viruses in dermal or subdermal tissues can reach nearby blood vessels, lymphatics, and neurons, conduits that enable systemic transmission (Box 2.2).

Figure 2.4 Sites of viral entry into the host. The body is covered with skin, which has a relatively impermeable (dead) outer layer of keratinocytes covering a layer of live epithelial cells rich in capillaries. Breaches in the integrity of the skin may allow viruses (or other microbes) access to this rich source of living cells. Moreover, other portals in the host, present to absorb food or release waste (mouth, urogenital tract, anus), exchange gases (respiratory tract), or interact with the environment (eyes), can also be entry points to allow access of viruses to host tissues.

The body’s response to a breach in the critical barrier formed by the skin is to make rapidly a hard, water-resistant shell over the wound, called a scab. Scabs are more than just the dermis below the site of injury drying and hardening; neutrophils and macrophages are recruited in large numbers to a wound, primarily to engulf bacteria and other pathogens that may benefit from this breach in the skin to infect the host. In addition, macrophages further aid the healing process by producing growth factors that promote cell proliferation. As the air dries the wound area, these formerly useful immune cells become part of the scab as well.

Figure 2.5 Schematic diagram of the skin. The epidermis consists of a layer of dead, keratinized cells over the live epidermal cells. Below this is the basement membrane (basal lamina). Below the basement membrane lies the dermis, which contains blood vessels, lymphatic vessels, fibroblasts, nerve endings, and macrophages. The potential depth reached by the proboscis of a mosquito taking a blood meal is shown. For more on how mosquitos spread viruses, see https://youtu.be/7wsk8a3ze80.