Basic Virology. Martinez J. Hewlett

infection or reactivation lead to encephalitis are unknown, but a lack of effective immunity appears to be a major factor. Certainly, there is a much higher risk of invasive HSV encephalitis in neonates and infants with primary HSV infection prior to full development of their own immune defenses. If diagnosed during early clinical manifestations of disease, HSV encephalitis can be treated effectively with antiviral drugs (see Chapter 8, Part II). But within a short period of time (a few days at most), infection leads to massive necrotic destruction of brain tissue, coma, and death.

      Although clinical isolates of HSV are often high in neurovirulence and neuroinvasive indices when they are tested in laboratory animals, there is no evidence that the virus recovered from patients with herpes encephalitis is any more virulent than those isolated from the more common, localized facial or genital infections. Moreover, there has never been any confirmed epidemiological pattern to the occurrence of herpes encephalitis that would suggest a specific strain of virus as a causative factor.

Viral encephalitis with favorable prognosis for recovery

      Many of the viruses that cause encephalitis have RNA genomes and are carried by arthropod vectors from zoonoses, and human involvement is often incidental. Such viruses are often termed arboviruses, although this is an imprecise classification that includes two groups of viruses not closely related by other criteria.

      The symptoms of encephalitis in wild animals can be difficult to measure, but several equine encephalitis viruses are known to cause serious disease in horses. Often the symptoms of viral encephalitis in humans are drowsiness, mild malaise, and sometimes coma. These mosquito‐borne encephalitis viruses do not usually directly invade neural tissue itself, but rather infect supporting tissue. The host response to this infection and resulting inflammation lead to the observed neurological symptoms.

      Since tissue at the periphery of neural tissue is the primary target for such encephalitis virus infections, the infection can be resolved and complete recovery will ensue, provided that the host's immune defenses work properly. During the disease's symptomatic period, lethargy and malaise of infected individuals make them vulnerable to other environmental hazards, including infection with other pathogens. But provided these risks are avoided by means of proper care, the disease generally resolves.

      While humans are often accidental targets for encephalitis viruses, it is not clear that symptoms of the disease in humans have any major role in virus spread. As with all arthropod‐borne diseases, transmission is by arthropod ingestion of blood‐associated virus found during the viremic stage of animal infection, and the behavioral effects are incidental. Still, it may be that the lethargy manifested during active disease makes infected animals more easily bitten by arthropods, and perhaps this is a factor in natural transmission.

Viral infections of the liver (viral hepatitis)

Diseases of the liver hold a special place in many types of medicine, both because of the important physiological role of this organ and because all circulating blood and lymph pass through the liver frequently. A number of different and unrelated viruses target the liver; these are collectively known as hepatitis viruses. All hepatitis viruses cause liver damage that can be devastating to the infected host. Liver failure due to hepatitis virus infections is a major reason for liver transplantation. Furthermore, a number of these viruses establish persistent carrier states in which virus is present for many months or years following infection. Currently, there are five reasonably well‐characterized human hepatitis viruses: A, B, C, delta (D), and E. The severity of the disease caused and the sequelae vary with each.

Hepatitis A

      This virus is classified as a picornavirus, related to poliovirus. Hepatitis A virus (HAV) is spread by contaminated water or food, and causes a potentially severe but controllable loss of liver function and general malaise. Proper medical care will generally result in full recovery of liver function and full clearance of virus from the host, with effective immunity against reinfection. A relatively effective HAV vaccine is available for individuals at risk of infection, including those who live in, or travel to, endemic regions.

Hepatitis B

      Hepatitis B virus is related to but clearly distinct from retroviruses. Unlike the situation with HAV, the B virus is spread mainly through blood, either during sexual activity or during other blood contamination events (sharing of needles, for instance), and primary infection is sometimes followed by persistent viremia and liver damage. Hepatitis B infection is a special risk to medical personnel owing to the possibility of transmission by needle stick from contaminated blood, and the virus is endemic among intravenous drug users, commercial sex workers, and their customers. The disease is also endemic in Southeast Asia, where the virus can be spread from mother to infant by birth trauma.

      Hepatitis B virus infection can lead to acute disease with attendant liver failure or can be asymptomatic. In many cases, virus is completely cleared, leading to full or partial recovery of liver function. Unfortunately, 5–10% of infected individuals go on to become asymptomatic chronic carriers of the virus. Indeed, chronic hepatitis B infections are a leading factor in human liver cancer. A third form of the hepatitis B virus infection (fulminant infection) is marked by rapid onset of extensive liver damage and often death. An effective vaccine against hepatitis B virus is now widely used to prevent infection.

Hepatitis C

      Hepatitis C virus is a member of the Flaviviridae, as are several other important human pathogens including dengue virus, Zika virus, and West Nile virus. The virus is transmitted by contaminated blood and blood products, and it is thought to cause as much as 25% of acute viral hepatitis worldwide. There is no current evidence of its being efficiently spread by arthropod vectors, but this possibility cannot be ruled out. Unlike those infected with HAV, a significant proportion of victims do not mount an effective immune response to the infection and have chronic infection that can last for many years with resulting accumulated liver damage and carcinoma. New anti–hepatitis C virus medicines introduced since 2011 have greatly improved the prognosis for infected people, but no vaccine currently exists.

Hepatitis delta (D)

      Hepatitis delta (D) virus is a defective virus that cannot replicate without the aid of another virus, the hepatitis B virus. Rates of hepatitis D and B virus coinfection vary widely throughout the world. Hepatitis D and B virus coinfection in the same individual, however, leads to a higher incidence of chronic liver disease than does infection with hepatitis B virus alone. Hepatitis D virus infection can be prevented by use of the hepatitis B vaccine, since hepatitis D virus replication is dependent on the presence of hepatitis B virus.

Hepatitis E

      Like HAV, hepatitis E virus is spread in the developing world by contaminated water and possibly by food. It is found throughout the world and has caused significant epidemics in India and Russia through problems with drinking water. In the developed world, hepatitis E virus is spread from animal reservoirs, primarily domestic pigs. The disease caused by this virus is usually mild, but can have high mortality rates in pregnant women. Recovery from acute infection is generally complete. Chronic infection occurs in immune‐compromised individuals.

QUESTIONS FOR CHAPTER 4

      1 The disease SSPE is a complication that may follow infection with measles virus. Discuss the possible mechanisms occurring during development of this rare disease.

      2 What features of pathogenesis are shared by measles