Paramyxoviridae

| INTRODUCTION | HISTORICAL NOTES | CLASSIFICATION AND TAXONOMY | PROPERTIES OF PARAMYXOVIRIDAE| HUMAN VIRUSES AND DISEASES | THERAPY | VACCINATION | USEFUL WEB LINKS | REFERENCES |

INTRODUCTION

The human paramyxoviruses are important pathogens of humans and are a common cause of respiratory disease in children. Approximately half of the cases of infantile bronchiolitis, croup, and pneumonia are caused by parainfluenza and respiratory syncytial viruses. Although measles and mumps used to be a signifcant problem worldwide, their incidence has decreased greatly in developed nations due to the success of immunization campaigns. However, measles remains to be a major cause of death among malnourished infants in the developing world - it is estimated that over a million children die annually of this disease in Third World countries.

HISTORICAL NOTES

Measles infection was distinguished from smallpox as early as the 9th century by an Arab physician by the name of Abu Becr (or Rhazes of Baghdad). However, there is no record of repeated epidemics identified as measles until the 11th and 12th centuries. Measles was first mentioned as a childhood disease in 1224. The Danish physician Peter Panum is generally given credit for illuminating the basic principles of measles infection and epidemiology during his trip to the Faroe Islands in 1846 during a measles epidemic.

Mumps was recognized as early as the 5th century B.C. by Hippocrates who described a mild epidemic illness involving swelling near the ears, sometimes painful swelling of one or both testes. In the 18th century, a physician first associated the central nervous system with mumps infection. One final note of interest, it is believed that the name "mumps" comes from an old English verb meaning "to grimace, grin, or mumble."

Both the parainfluenza viruses and respiratory syncytial virus (RSV) were not isolated until fairly recently. The four human parainfluenza viruses were recognized between 1956 and 1960. RSV was first isolated in 1956 from a symptomatic lab chimp during an outbreak of cold-like illnesses. Soon after this incident, RSV was isolated from one child with pneumonia and one child with croup in Baltimore.

CLASSIFICATION AND TAXONOMY

The Paramyxoviridae family was reclassified into two subfamilies, Paramyxovirinae and Pneumovirinae, by the International Committee on Taxonomy of Viruses in 1993. The following classification system is based on differences in the organization of the genome, the sequence relationship of the encoded proteins, the biological activity of the proteins, and morphological characteristics.

PARAMYXOVIRIDAE TAXONOMY

Subfamily	Genus	Human Species
Paramyxovirinae	Paramyxovirus	Human parainfluenza viruses types 1 and 3
	Rubulavirus	Human parainfluenza viruses types 2, 4a, and 4b; mumps virus
	Morbillivirus	Measles virus
Pneumovirinae	Pneumovirus	Human respiratory syncytial virus

PROPERTIES OF PARAMYXOVIRIDAE

Genome contains linear minus sense ssRNA, 15-16 kb

Helical nucleocapsid, NP or (N) protein associated with transcriptase (L) and phosphoprotein (P)

Enveloped, fusion protein (F) and attachment protein hemaglutinin- neuraminidase (HN) or hemaglutinin (H) or neither activity (G); also contains nonglycosylated membrane protein (M)

Cytoplasmic replication

Buds from the plasma membrane

HUMAN VIRUSES AND DISEASES ASSOCIATED WITH THIS FAMILY

The major human viruses of the Paramyxoviridae family are: measles virus, mumps virus, the parainfluenza viruses (types 1, 2, 3, 4a, and 4b), and respiratory syncytial virus (RSV).

All of the viruses of the Paramyxoviridae family are spread through the respiratory route and are highly contagious.

Disease caused by the measles virus is typically marked by a prodrome of fever, conjunctivitis, coryza, and cough which is followed by the development of a rash of flat maculeswhich first appear on the head and then move to the chest, trunk, and limbs. These macules typically fuse resulting in large blotches that can be slow to fade. Two serious complications of measles infection are acute postinfectious encephalitis, which occurs in about 1 in every 1,000 cases, and subacute sclerosing panencephalitis (SSPE), which occurs in about 1 in every 300,000 cases. Postinfectious encephalitis usually develops during the first week following development of the rash, has a mortality rate of 15%, and survivors typically have neurologic sequelae. SSPE, on the other hand, develops years (typically 7-10) following infection with the measles virus and is always fatal.

Infection with mumps virus typically results in a minor illness characterized by parotitis, or inflammation of the salivary glands. However, mumps in postpubertal males can result in orchitis, or inflammation of the testes, a painful condition which can result in destruction of the testicular tissue. Futhermore, mumps is the most common cause of meningitis. One serious, yet rare, complication of mumps infection is mumps encephalitis which can result in unilateral nerve deafness.

Parainfluenza viruses are common respiratory pathogens of humans that typically produce minor upper respiratory tract infections which are characterized by coryza, pharyngitis, low fever, and bronchitis. Parainfluenza viruses are also the most common cause of croup, or laryngotracheobronchitis, in children aged 6 months to 5 years. Croup is marked by fever, cough, respiratory distress, and stridor. In extreme cases, laryngeal obstruction can occur. Finally, parainfluenza viruses are also capable fo causing bronchiolitis and /or pneumonia in children under the age of 6 months. It should be noted that croup and pneumonia occur in only 2-3% of cases.

Respiratory syncytial virus (RSV) is an important human pathogen of infants. Although it typically presents as a febrile rhinitis and/or pharyngitis and commonly involves the inner ear, RSV does cause severe illness in about 1% of all babies. Severe RSV infection is characterized by a pronounced cough and wheezing which eventually deveops into dyspnea and a high respiratory rate and hypoxemia. Death occur in about 1% of infants who develop serious illness. Death can occur very quickly and therefore might partially explain the phenomenon of sudden infant death syndrome. Finally, it should be noted that the elderly and immunosuppressed transplant patients are at risk for developing pneumonia due to RSV infection.

There is no standard antiviral treatment for measles although ribavirin (1 fl-D-ribofuranosyl-1,2,4-triazole- 3-carboxamide) has been shown to decrease viral replication in vivo and might decrease the severity of acute measles. Perhaps the most promising treatment for measles infection is the administration of high doses of vitamin A. Vitamin A supplements have been shown to decrease both the morbidity and mortality of acute measles, even if the individual is not suffering from a vitamin A deficiency. Finally, numerous agents have been suggested for therapeutic treatment of SSPE but it is extremely difficult to determine their efficacy because SSPE is rare and the benefits of such treaments would only be short-term.

Treatment for mumps generally involves symptomatic treatment although it has been suggested that immunotherapy consisting of high-titer polyvalent or monoclonal antibody preparations could be used in some cases during the early course of the disease.

Like measles, there is no specific antiviral treatment for infection with parainfluenza viruses although in vitro experiments suggest that ribavirin might have some therapeutic benefits. Treatment of croup often involves air humidification and inhalation of racemic epinephrine. Severe croup is treated with large doses of systemic corticosteroids.

Ribavirin has been shown to be effective in the treatment of RSV infection. While administration by small-particle aerosol has little or no systemic toxicity, oral administration has been associated with mild bone marrow and hepatic toxicity. Treatment of RSV infection also involves supportive care such as proper positioning of the infant, air humidification, and removal of secretion. Wheezing might require the administration of adrenergic drugs and severe cases may require respiratory assistance. Finally, there is some evidence that human intravenous IgG (IVIG) therapy might be effective.

VACCINATION

A live attenuated mumps vaccine was introduced in the United States in 1967. Since the introduction of the vaccine there has been a steady decline in the number of mumps cases (it has declined from 76 per 100,000 in 1968 to approximately 1 or 2 per 100,000). A live attenuated vaccine also exists for the measles virus. Seroconversion occurs in 95-98% of individuals who are immunized at about 15 months of age. Although an effective vaccine exists, there has been an increase in measles cases since 1983 among college students (which is probably a result of waning immunity) and preschool infants of racial and ethnic minorities (which is partially due to unimmunized immigrants). The Centers for Disease Control and Prevention has Web pages that provide complete information regarding measles immunization and mumps immunization.

A recent clinical trial has shown that a live bovine parainfluenza type 3 (BPIV-3) vaccine is effective in infants under the age of 6 months. Likewise a recent clinical trial of a RSV subunit vaccine (PFP-2) made from the purified fusion glycoprotein of the A2 strain of RSV has shown that the vaccine was immunogenic in the frail, institutionalized elderly. Thus, it appears as though great progress is being made in the development of a vaccine against these two common respiratory pathogens.

USEFUL WEB LINKS

Electron micrograph pictures of viruses in the Paramyxoviridae family.

For everything you ever wanted to know about virology, check out the Garry Lab web site.

Collins, P.L., Chanock, R.H., and McIntosh, K. (1996). Parainfluenza viruses. In "Field's Virology", (B.N. Fields, D.M. Knipe, P.M. Howley, R.M. Chanock, J.L. Melnick, T.P. Monath, B. Roizman, and S.E. Straus, eds.), 3rd Edition. Lippincott-Raven, Philadelphia, PA. pp. 1205-1241.

Collins, P.L., Chanock, R.H., and McIntosh, K. (1996). Respiratory syncytial virus.In "Field's Virology", (B.N. Fields, D.M. Knipe, P.M. Howley, R.M. Chanock, J.L. Melnick, T.P. Monath, B. Roizman, and S.E. Straus, eds.), 3rd Edition. Lippincott-Raven, Philadelphia, PA. pp. 1313-1351.

Falsey, A.R., and Walsh, E.E. (1997). Safety and immunogenicity of a respiratory syncytial virus subunit vaccine (PFP-2) in the institutionalized elderly. Vaccine. 15: 1130-1132.

Griffin, D.E., and Bellini, W.J. (1996). Measles virus. In "Field's Virology", (B.N. Fields, D.M. Knipe, P.M. Howley, R.M. Chanock, J.L. Melnick, T.P. Monath, B. Roizman, and S.E. Straus, eds.), 3rd Edition. Lippincott- Raven, Philadelphia, PA. pp. 1267-1312.

Karron, R.A., Makhene, M., Gay, K., wilson, M.H., Clements, M.L., and Murphy, B.L. (1996). Evaluation of a live attenuated bovine parainfluenza type 3 vaccine in two- to six-month-old infants. Pediatric Infectious Disease Journal. 15: 650-654.

Lamb, R.A. and Kolakofsky, D. (1996). Paramyxoviridae: The Viruses and Their Replicaiton. In "Field's Virology", (B.N. Fields, D.M. Knipe, P.M. Howley, R.M. Chanock, J.L. Melnick, T.P. Monath, B. Roizman, and S.E. Straus, eds.), 3rd Edition. Lippincott-Raven, Philadelphia, PA. pp. 1177-1204.

Wolinsky, J.S. (1996). Mumps virus. In "Field's Virology", (B.N. Fields, D.M. Knipe, P.M. Howley, R.M. Chanock, J.L. Melnick, T.P. Monath, B. Roizman, and S.E. Straus, eds.), 3rd Edition. Lippincott-Raven, Philadelphia, PA. pp. 1234-1265.

White, D.O., and Fenner, F.J. (1994). "Medical Virology", 4th Edition. Academic Press, San Diego, CA. pp. 456-474.

Web Page Created By: Jennifer Trayner

Humans and Viruses
Human Biology115A
Winter, 1998
Robert Siegel, instructor

Created: February 10, 1998
Last Modified: March 4, 1998