Principles of Virology, Volume 2. S. Jane Flint

disease.” Remarkably, the incubation time for this virus (that is, the time between infection and disease) is 4 to 7 weeks. Consequently, an Epstein-Barr virus-infected Lothario has lots of time to transmit far more than a radiant smile and magnetic personality before being “found out.” Human cytomegalovirus, mumps virus, and some retroviruses can also be transmitted by means of saliva exchange.

Feces

      Particles of enteric and hepatic viruses that are shed into the intestine and transmitted via a fecal route are generally more resistant to inactivation by environmental conditions than those released at other sites. Viruses transmitted by fecal spread usually survive dilution in water, as well as drying. An important exception is hepatitis B virus, which is shed in bile that is released into the intestine, but is inactivated as a consequence and therefore not transmitted in feces.

      Inefficient sewage treatment or its absence, contaminated irrigation systems, and the use of animal manures are prime sources of fecal contamination of food, water supplies, and living areas. Any one of these conditions provides an effective mode for continual reentry of these viruses into the alimentary canals of new hosts, the so-called “fecal-oral route.” Two hundred years ago, such contamination was inevitable in most of the world, as disposal of human feces in the streets was a common practice. Communities downstream of sites of defecation and waste removal used contaminated water for cooking and drinking. With modern sanitation, the fecal-oral cycle has been largely interrupted in developed countries, but it remains a major cause of viral spread throughout the rest of the world.

BOX 2.12

      DISCUSSION

       A ferret model of influenza virus infection ignites irrational fears

      Ferrets, which are carnivorous mammals, are excellent models for the study of influenza virus infection, pathogenesis, and transmission. Human and avian influenza viruses reproduce in the ferret airway, and infected animals develop many characteristic signs of the flu, including fever and sneezing. The release of infectious virus through nasal discharges allows for ferret-to-ferret transmission of influenza, an observation first reported in 1933.

      In 2011, influenza virus experiments using this well-established model came under intense media scrutiny when two research groups genetically engineered an H5N1 strain of influenza virus that was suspected to have pandemic potential in humans. These investigators showed that the engineered viruses were transmissible in ferrets, raising concerns that, if the viruses or an infected ferret escaped or was otherwise released, a new influenza pandemic could be triggered. The debate, which continues to impact the scientific and lay communities, centers around “dual-use” experiments: studies that have both a potential public health benefit but that could also be used for bioterrorism or could endanger humans. Some scientists have contended that work such as this should never have been done, given the risks. Others, including many virologists, counter with multiple points. First, that a virus can be transmitted in ferrets does not indicate that it will also spread in humans. However, knowing the genetic changes that affect transmission would have great benefit should an H5N1 virus infection occur in humans. Moreover, high-level biocontainment facilities and procedures for performing such experiments safely are in place to prevent accidental release of nefarious viruses (or infected animals). While it may seem like the basis of an exciting thriller, work with these agents is strictly controlled.

       Belser JA, Katz JM, Tumpey TM. 2011. The ferret as a model organism to study influenza A virus infection. Dis Model Mech 4:575–579.

Blood

      Viremia is a common feature of many viral infections, and exposure to viremic blood is a primary mode of virus trans mission. Insects acquire virus particles when they bite viremic hosts and may transmit them to subsequent hosts with the next blood meal. This, however, is not true for all blood-borne viruses: for example, human immunodeficiency virus type 1 cannot be transmitted by mosquitos. Hepatitis viruses and human immunodeficiency virus type 1 can be transmitted by virus-laden blood during transfusions and injections. Virus particles may also be transmitted from blood during sexual intercourse or childbirth, and consumption of raw meat may place contaminated blood in contact with the alimentary canal and respiratory tract. Health care professionals, emergency rescue workers, and dentists are exposed routinely to blood from individuals who may harbor infections. Indeed, for many of the viruses that cause fatal hemorrhagic fevers (such as members of the Bunyaviridae and Filoviridae), the primary mode of transmission to humans is via contaminated blood and body fluids. Consequently, health care workers often are among the first to become infected and show symptoms in an outbreak of such viral diseases.

Urine

      Virus-containing urine is a common contaminant of food and water supplies. The presence of virus particles in the urine is called viruria. Hantaviruses and arenaviruses that infect rodents cause persistent viruria. Consequently, humans may be infected by exposure to dust that contains dried urine from infected rodents. A few human viruses, including the polyomaviruses JC and BK, and the prevalent herpesvirus, cytomegalovirus, reproduce in the kidneys and are shed in urine.

Semen

      Some retroviruses, including human immunodeficiency virus type 1, herpesviruses, and hepatitis B virus, are shed in semen and are transmitted during sex. Herpesviruses that infect the genital mucosa are shed from lesions and transmitted in genital secretions, as are papillomaviruses. Though Zika virus is primarily transmitted by mosquito, a surprising observation was that it is also detected in the semen of infected males, where it can remain replication-competent for up to 6 months. Most viruses found in semen reproduce in testicular tissue, from which they are shed into the seminal fluid.

Milk

      Mouse mammary tumor virus is transmitted to offspring primarily via mother’s milk into which the virus is shed, as are some tick-borne encephalitis viruses. Mumps virus and cytomegalovirus are shed into human milk but are probably not often transmitted by this route. Importantly, transmission of human immunodeficiency virus type 1 through breastfeeding is responsible for more than half of new pediatric infections with this virus. Breast milk contains components with anti-infectious, immunomodulatory, or anti-inflammatory properties that can regulate both viral reproduction and infant susceptibility. Even during antiretroviral therapy, a stable, CD4⁺ T cell-associated reservoir of human immunodeficiency virus type 1 is persistently present in breast milk, a likely source of infection. Only prophylactic treatment in infants is likely to protect human immunodeficiency virus type 1-exposed babies against all forms of transmission from breast milk.

Skin Lesions

Many viruses reproduce in the skin, and the lesions that form from such infections contain virions that can be transmitted to other hosts. In these cases, the virus is usually transmitted by direct body contact. For example, herpes simplex virus causes a common rash in wrestlers, known as herpes gladiatorum or “mat herpes” (Fig. 2.22). Certain poxviruses and papillomaviruses that cause warts may also be transmitted by direct, skin-to-skin contact.

Varicella-zoster virus, the agent of chicken pox, is released from the skin in a particularly effective manner. The lesions that form during an acute chicken pox infection are small, lymph-filled blisters that erupt, leaving a crusty scab. Virus concentrations in this fluid are high. Despite the avail ability of an effective vaccine, acute infections still occur in unvaccinated individuals. Alarmingly, some parents have elected to allow their children to become infected by encouraging close exposure to acutely infected peers (