These viruses are presented in alphabetical order. They are listed in Table 46–1 in terms of their nucleic acid and presence of an envelope.
Characteristics Representative Viruses
DNA enveloped viruses
DNA nonenveloped viruses
RNA enveloped viruses
Herpes B virus, human herpesvirus 6, poxviruses of animal origin (cowpox virus, monkeypox virus)
None
Cache Valley virus, chikungunya virus, Ebola virus, hantaviruses, Hendra virus, human metapneumovirus,
Japanese encephalitis virus, Lassa fever virus, lymphocytic choriomeningitis virus, Nipah virus, Marburg virus, spumaviruses, Tacaribe complex of viruses (e.g., Junin and
Machupo viruses), Whitewater Arroyo virus
RNA nonenveloped viruses
Astroviruses, encephalomyocarditis virus
Astroviruses are nonenveloped RNA viruses similar in size to polioviruses. They have a characteristic five- or six-pointed morphology. These viruses cause watery diarrhea, especially in children. Most adults have antibodies against astroviruses, suggesting that infection occurs commonly. No antiviral drugs or preventive measures are available.
This virus was first isolated in Utah in 1956 but is found throughout the western hemisphere. It is a bunyavirus transmitted by Aedes,
Anopheles, orCuliseta mosquitoes from domestic livestock to people. It is a rare cause of encephalitis in humans. There is no treatment or vaccine for Cache
Valley virus infections.

This virus causes chikungunya fever characterized by the sudden onset of high fever and joint pains, especially of the wrists and ankles. A macular or maculopapular rash over much of the body is common. Outbreaks involving millions of people in India, Africa, and the islands in the Indian Ocean have occurred in the years from 2004 to 2006.
Chikungunya virus is an RNA enveloped virus and is a member of the Togavirus family. It has a single-stranded, positive-polarity RNA genome. It is transmitted by species of Aedes mosquitoes, both A. aegypti and A. albopictus. The latter mosquito is found in the United States so the potential for outbreaks exists.
Individuals returning to the United States from areas where outbreaks have occurred have been diagnosed with chikungunya fever. Laboratory diagnosis involves detecting the virus in blood either by culturing or by ELISA assays.
Antibody tests for either IgM or for a rise in titer of IgG can also be used to make a diagnosis. There is no antiviral therapy and no vaccine is available.
Ebola virus is named for the river in Zaire that was the site of an outbreak of hemorrhagic fever in 1976. The disease begins with fever, headache, vomiting, and diarrhea. Later, bleeding into the gastrointestinal tract occurs, followed by shock and disseminated intravascular coagulation. The hemorrhages are caused by severe thrombocytopenia. The mortality rate associated with this virus approaches 100%. Most cases arise by secondary transmission from contact with the patient's blood or secretions, e.g., in hospital staff. Reuse of needles and syringes is also implicated in the spread within hospitals. Although greatly feared,
Ebola hemorrhagic fever is quite rare. As of this writing, approximately 1000 cases have occurred since its appearance in 1976.
Ebola virus is a member of the filovirus family. The appearance of filoviruses (filothread) is unique. They are the longest viruses, often measuring thousands of nanometers. (see Color Plate 32). The natural reservoir of Ebola virus is unknown. Monkeys can be infected but, because they become sick, are unlikely to be the reservoir. Bats are suspected of being the reservoir but this has not been established. The high mortality rate of Ebola virus is attributed to several viral virulence factors: its glycoprotein kills endothelial cells, resulting in hemorrhage, and two other proteins inhibit the induction and action of interferon.
Lymphocytes are killed and the antibody response is ineffective.

Ebola virus—Electron micrograph. Long arrow points to a typical virion of Ebola virus.
Short arrow points to the "shepherd's crook" appearance of some Ebola virions. Provider:
CDC/Dr. Erskine Palmer and Dr. Russell Regnery.
Diagnosis is made by isolating the virus or by detecting a rise in antibody titer.
(Extreme care must be taken when handling specimens in the laboratory.) No antiviral therapy is available. Prevention centers on limiting secondary spread by proper handling of patient's secretions and blood. There is no vaccine.
Hantaviruses are members of the bunyavirus family. The prototype virus is
Hantaan virus, the cause of Korean hemorrhagic fever (KHF). KHF is characterized by headache, petechial hemorrhages, shock, and renal failure. It occurs in Asia and Europe but not North America and has a mortality rate of about 10%. Hantaviruses are part of a heterogeneous group of viruses called roboviruses, which stands for "rodent-borne" viruses. Roboviruses are transmitted from rodents directly (without an arthropod vector), whereas arboviruses are "arthropod-borne."
In 1993, an outbreak of a new disease, characterized by influenza-like symptoms followed rapidly by acute respiratory failure, occurred in the western United
States, centered in New Mexico and Arizona. This disease, now called hantavirus pulmonary syndrome, is caused by a hantavirus (Sin Nombre virus) endemic in deer mice (Peromyscus) and is acquired by inhalation of aerosols of the rodent's urine and feces. It is not transmitted from person to person. Very few people have antibody to the virus, indicating that asymptomatic infections are not common. The diagnosis is made by detecting viral RNA in lung tissue with the

polymerase chain reaction (PCR) assay, by performing immunohistochemistry on lung tissue, or by detecting IgM antibody in serum. The mortality rate of hantavirus pulmonary syndrome is very high, approximately 38%. As of June
2003, a total of 339 cases of hantavirus pulmonary syndrome have been reported in the United States. Most cases occurred in the states west of the Mississippi, particularly in New Mexico, Arizona, California, and Colorado, in that order.
There is no effective drug; ribavirin has been used but appears to be ineffective.
There is no vaccine for any hantavirus.
This virus was first recognized as a human pathogen in 1994, when it caused severe respiratory disease in Hendra, Australia. It is a paramyxovirus resembling measles virus and was previously called equine morbillivirus. The human infections were acquired by contact with infected horses, but fruit bats appear to be the natural reservoir. There is no treatment or vaccine for Hendra virus infections.
This virus (monkey B virus or herpesvirus simiae) causes a rare, often fatal encephalitis in persons in close contact with monkeys or their tissues, e.g., zookeepers or cell culture technicians. The virus causes a latent infection in monkeys that is similar to herpes simplex virus (HSV)-1 infection in humans.
Herpes B virus and HSV-1 cross react antigenically, but antibody to HSV-1 does not protect from herpes B encephalitis. The presence of HSV-1 antibody can, however, confuse serologic diagnosis by making the interpretation of a rise in antibody titer difficult. The diagnosis can therefore be made only by recovering the virus. Acyclovir may be beneficial. Prevention consists of using protective clothing and masks to prevent exposure to the virus. Immune globulin containing antibody to herpes B virus should be given after a monkey bite.
This herpesvirus is the cause of exanthem subitum (roseola infantum), a common disease in infants that is characterized by a high fever and a transient rash. The virus is found worldwide, and up to 80% of people are seropositive. The virus is lymphotropic and infects both T and B cells. It remains latent within these cells but can be reactivated in immunocompromised patients and cause pneumonia.
Many virologic and clinical features of HHV-6 are similar to those of cytomegalovirus, another member of the herpesvirus family.
This paramyxovirus was first reported in 2001 as a cause of severe bronchiolitis and pneumonia in young children in the Netherlands. It is similar to respiratory syncytial virus (also a paramyxovirus) in the range of respiratory tract disease it causes. Serologic studies showed that most children have been infected by 5

years of age and that this virus has been present in the human population for at least 50 years.
This virus is the most common cause of epidemic encephalitis. The disease is characterized by fever, headache, nuchal rigidity, altered states of consciousness, tremors, incoordination, and convulsions. The mortality rate is high, and neurologic sequelae are severe and can be detected in most survivors. The disease occurs throughout Asia but is most prevalent in Southeast Asia. The rare cases seen in the United States have occurred in travelers returning from that continent. American military personnel in Asia have been affected.
Japanese encephalitis virus is a member of the flavivirus family. It is transmitted to humans by certain species of Culex mosquitoes endemic to Asian rice fields.
There are two main reservoir hosts—birds and pigs. The diagnosis can be made by isolating the virus, by detecting IgM antibody in serum or spinal fluid, or by staining brain tissue with fluorescent antibody. There is no antiviral therapy.
Prevention consists of an inactivated vaccine and pesticides to control the mosquito vector. Immunization is recommended for individuals living in areas of endemic infection for several months or longer.
Lassa fever virus was first seen in 1969 in the Nigerian town of that name. It causes a severe, often fatal hemorrhagic fever characterized by multiple-organ involvement. The disease begins slowly with fever, headache, vomiting, and diarrhea and progresses to involve the lungs, heart, kidneys, and brain. A petechial rash and gastrointestinal tract hemorrhage ensue, followed by death from vascular collapse.
Lassa fever virus is a member of the arenavirus family, which includes other infrequent human pathogens such as lymphocytic choriomeningitis virus and certain members of the Tacaribe group. Arenaviruses ("arena" means sand) are united by their unusual appearance in the electron microscope. Their most striking feature is the "sandlike" particles on their surface, which are ribosomes.
The function, if any, of these ribosomes is unknown. Arenaviruses are enveloped viruses with surface spikes, a helical nucleocapsid, and single-stranded RNA with negative polarity.
The natural host for Lassa fever virus is the small rodent Mastomys, which undergoes a chronic, lifelong infection. The virus is transmitted to humans by contamination of food or water with animal urine. Secondary transmission among hospital personnel occurs also. Asymptomatic infection is widespread in areas of endemic infection.
The diagnosis is made either by isolating the virus or by detecting a rise in antibody titer. Ribavirin reduces the mortality rate if given early, and

hyperimmune serum, obtained from persons who have recovered from the disease, has been beneficial in some cases. No vaccine is available, and prevention centers on proper infection control practices and rodent control.
Lymphocytic choriomeningitis virus is a member of the arenavirus family. It is a rare cause of aseptic meningitis and cannot be distinguished clinically from the more frequent viral causes, e.g., echovirus, coxsackievirus, or mumps virus. The usual picture consists of fever, headache, vomiting, stiff neck, and changes in mental status. Spinal fluid shows an increased number of cells, mostly lymphocytes, with an elevated protein level and a normal or low sugar level.
The virus is endemic in the mouse population, in which chronic infection occurs.
Animals infected transplacentally become healthy lifelong carriers. The virus is transmitted to humans via food or water contaminated by mouse urine or feces.
There is no human-to-human spread: i.e., humans are accidental dead-end hosts although transmission of the virus via solid organ transplants has occurred. In
2005, seven of eight transplant recipients who became infected, died. Diagnosis is made by isolating the virus from the spinal fluid or by detecting an increase in antibody titer. No antiviral therapy or vaccine is available.
This disease is the prototype used to illustrate immunopathogenesis and immune-complex disease. If immunocompetent adult mice are inoculated, meningitis and death ensue. If, however, newborn mice or x-irradiated immunodeficient adults are inoculated, no meningitis occurs despite extensive viral replication. If sensitized T cells are transplanted to the immunodeficient adults, meningitis and death occur. The immunodeficient adult mice, who are apparently well, slowly develop immune-complex glomerulonephritis. It appears that the mice are partially tolerant to the virus in that their cell-mediated immunity is inactive, but sufficient antibody is produced to cause immune complex disease.
Marburg virus and Ebola virus are similar in that they both cause hemorrhagic
fever and are members of the filovirus family; however, they are antigenically distinct. Marburg virus was first recognized as a cause of human disease in 1967 in Marburg, Germany. The common feature of the infected individuals was their exposure to African green monkeys that had recently arrived from Uganda. As with Ebola virus, the natural reservoir of Marburg virus is unknown.
The clinical picture of this hemorrhagic fever is as described for Ebola virus (see
Ebola Virus). In 2005, an outbreak of hemorrhagic fever caused by Marburg virus killed hundreds of people in Angola. No cases of disease caused by either Ebola or
Marburg virus have occurred in the United States.

The diagnosis is made by isolating the virus or detecting a rise in antibody titer.
No antiviral therapy or vaccine is available. As with Ebola virus, secondary cases among medical personnel have occurred; therefore, stringent infection control practices must be instituted to prevent nosocomial spread.
Nipah virus is a paramyxovirus that caused encephalitis in Malaysia and
Singapore in 1998 and 1999. People who had contact with pigs were particularly at risk for encephalitis caused by this previously unrecognized virus. There is no treatment or vaccine for Nipah virus infections.
Four poxviruses cause disease in animals and also cause poxlike lesions in humans on rare occasions. They are transmitted by contact with the infected animals, usually in an occupational setting.
Cowpox virus causes vesicular lesions on the udders of cows and can cause similar lesions on the skin of persons who milk cows. Pseudocowpox virus causes a similar picture but is antigenically distinct. Orf virus is the cause of contagious pustular dermatitis in sheep and of vesicular lesions on the hands of sheepshearers.
Monkeypox virus is different from the other three; it causes a human disease that resembles smallpox. It occurs almost exclusively in Central Africa. In 2003, an outbreak of monkeypox occurred in Wisconsin, Illinois, and Indiana. In this outbreak, the source of the virus was animals imported from Africa. It appears that the virus from the imported animals infected local prairie dogs, which then were the source of the human infection. None of those affected died. In Africa, monkeypox has a death rate of between 1% and 10%, in contrast to 50% for smallpox. There is no effective antiviral treatment. The vaccine against smallpox appears to have some protective effect against monkeypox.
Any new case of smallpoxlike disease must be precisely diagnosed to ensure that it is not due to smallpox virus. There has not been a case of smallpox in the world since 1977, 1 and smallpox immunization has been allowed to lapse.
For these reasons, it is important to ensure that new cases of smallpoxlike disease are due to monkeypox virus. Monkeypox virus can be distinguished from smallpox virus in the laboratory both antigenically and by the distinctive lesions it causes on the chorioallantoic membrane of chicken eggs.
1 With the exception of two laboratory-acquired cases in 1978.
Spumaviruses are a subfamily of retroviruses that cause a foamy appearance in cultured cells. They can present a problem in the production of viral vaccines if

they contaminate the cell cultures used to make the vaccine. There are no known human pathogens.
The Tacaribe 2 complex contains several human pathogens, all of which cause hemorrhagic fever.
The best known are Sabia virus in Brazil, Junin virus in Argentina, and Machupo virus in Bolivia. Hemorrhagic fevers, as the name implies, are characterized by fever and bleeding into the gastrointestinal tract, skin, and other organs. The bleeding is due to thrombocytopenia. Death occurs in up to 20% of cases, and outbreaks can involve thousands of people. Agricultural workers are particularly at risk.
Similar to other arenaviruses such as Lassa fever virus and lymphocytic choriomeningitis virus, these viruses are endemic in the rodent population and are transmitted to humans by accidental contamination of food and water by rodent excreta. The diagnosis can be made either by isolating the virus or by detecting a rise in antibody titer. In a laboratory-acquired Sabia virus infection, ribavirin was an effective treatment. No vaccine is available.
2 Tacaribe virus was isolated from bats in Trinidad in 1956. It does not cause human disease.
This virus is the cause of a hemorrhagic fever/acute respiratory distress syndrome in the western part of the United States. It is a member of the arenavirus family, as is Lassa fever virus, a cause of hemorrhagic fever in Africa
(see Lassa Fever Virus). Wood rats are the reservoir of this virus, and it is transmitted by inhalation of dried rat excrement. This mode of transmission is the same as that of the hantavirus, Sin Nombre virus (see Hantaviruses). There is no established antiviral therapy and there is no vaccine.