Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Picornavirus-Overview

  • Author: Larry I Lutwick, MD; Chief Editor: Mark R Wallace, MD, FACP, FIDSA  more...
 
Updated: Dec 17, 2014
 

Background

The Picornaviridae family (picornaviruses) causes a wider range of illnesses than most other, if not all, virus families. Infection with various picornaviruses may be asymptomatic or may cause clinical syndromes such as aseptic meningitis (the most common acute viral disease of the CNS), encephalitis, the common cold, febrile rash illnesses (hand-foot-and-mouth disease), conjunctivitis, herpangina, myositis and myocarditis, and hepatitis.[1, 2]

Poliomyelitis, caused by the enteroviral type species, was one of the first recorded infections; an Egyptian tomb carving showed a man with a foot-drop deformity typical of paralytic poliomyelitis.

Characteristics

The term Picornaviridae is derived from pico, which means small (typically, 18-30 nm), and RNA, referring to the single-stranded positive-sense RNA common to all members of the Picornaviridae family.[3] All members of this family, whose RNA molecules range from 7.2-8.5 kilobases (kb) in size, lack a lipid envelope and are therefore resistant to ether, chloroform, and alcohol. However, ionizing radiation, phenol, and formaldehyde readily inactivate picornaviruses.

The viral capsid of picornaviruses consists of a densely packed icosahedral arrangement of 60 protomers. Each protomer consists of 4 polypeptides, etoposide (VP) 1, 2, 3, and 4, which all derive from the cleavage of a larger protein. The capsid-coat protein serves multiple functions, including (1) protecting the viral RNA from degradation by environmental RNAse, (2) determining host and tissue tropism by recognition of cell-specific cell-membrane receptors, (3) penetrating target cells and delivering the viral RNA into the cell cytoplasm, and (4) selecting and packaging viral RNA.[4]

Two genera of Picornaviridae— enterovirus and rhinovirus —have an identical morphology but can be distinguished based on clinical, biophysical, and epidemiological studies. Enteroviruses grow at a wide pH range (ie, 3-10). After initial replication in the oropharynx, enteroviruses survive the acidic environment of the stomach. The small intestine is the major invasion site of enteroviruses, which replicate best at 37°C. Rhinoviruses replicate at a pH of 6-8. After initial replication in the nasal passages, the acidic environment of the stomach destroys rhinoviruses. Rhinoviruses optimally replicate at 33°C and primarily infect the nasal mucosa.[5, 6]

Classification

Enteroviruses have several subgroups: 3 serotypes of polioviruses, 23 serotypes of group A coxsackieviruses, 6 serotypes of group B coxsackieviruses, and at least 31 serotypes of echoviruses. (ECHO virus is a misnomer based on the acronym enteric cytopathic human orphan virus.) Viruses are grouped according to pathogenicity, host range, and serotype, which is based on serum neutralization. Some enteroviruses are not classified further but rather assigned a number, currently 68 to 71. Bovine, equine, simian, porcine, and rodent enteroviruses also exist.

Overall, the family Picornaviridae includes 9 genera. In addition to the major human enteroviral pathogens (poliovirus, enterovirus, coxsackievirus, echovirus), rhinoviruses (approximately 105 serotypes), the human hepatitis A virus (HAV), and several parechoviruses, Picornaviridae contains several other genera of viruses that infect nonhuman vertebrate hosts.

Cardiovirus (type species, encephalomyocarditis virus) is a classic infection in mice, although it has been observed to cause disease in humans.[7] Certain strains of this virus are associated with the development of diabetes in certain strains of mice and are used as a model for virus-associated insulin-requiring diabetes in humans.

Aphthovirus (type species, foot-and-mouth disease virus [FMDV]) creates a major worldwide economic problem, particularly in South America and Australia. FMDV, which has 7 serotypes, is largely controlled by the immunization or slaughter of infected animals. Aphthoviruses are more acid-labile than other picornaviruses.

The other genera include Parechovirus, Erbovirus (equine rhinitis B virus), Kobuvirus (Aichi virus), and Teschovirus (porcine teschovirus). Arthropod-infecting viruses, including Cricket paralysis virus, Drosophila C virus, and Tussock moth virus, are additional unclassified picornaviruses.

Next

Pathophysiology

The pathogenesis of picornaviral infection is best understood for polioviruses, whose pathophysiology is similar to other picornaviruses except for tissue tropism after viremia. Of note, not all picornaviruses spread from the initial site of infection (eg, rhinoviruses).[8]

The replication cycle of picornaviruses is approximately 8 hours, with the exact duration depending on variables such as pH, temperature, cell type, and number of viral particles that infect the cell. The cycle proceeds in host cell cytoplasm, can occur in enucleated cells, and is not inhibited by actinomycin D. Although lytic infections are the rule, HAV can cause nonlytic infections that persist indefinitely.[9, 10]

Cellular protein synthesis declines precipitously after infection, possibly because of the interference with the 5' end of eukaryotic mRNA. A virus-encoded, RNA-dependent RNA polymerase, which produces negative-sense strands, copies the genomic RNA. These strands serve as templates for the positive-sense RNA synthesis.[9, 11]

In most picornaviral infections, infected cells growing in tissue culture show characteristic morphologic changes.[12] Within an hour of infection, margination of the chromatin occurs, in which normally homogeneous nuclear material begins to accumulate on the inside of the nuclear envelope. By 2.5-3 hours, membranous vesicles appear in the cytoplasm, beginning around the nuclear membrane and spreading outward. This vesiculation is associated with changes in the permeability of the cellular plasma membrane and eventual shriveling of the cell. Crystals of virus can be observed late in the process. The cytopathic effect appears mediated, at least in part, by a redistribution of lysosomal enzymes.

The antigenic structure of each viral capsid allows it to bind to specific cell membrane components. The virus uses these membrane receptors to enter the target cell. Different viruses use different identifiable receptors, and receptors may vary even among the same genus. For example, most human rhinoviruses bind to the intracellular adhesion molecule 1 (ICAM-1), an immunoglobulinlike molecule; others use a low-density lipoprotein receptor.[8] Families among the picornaviruses may use the same receptor, which may be shared by unrelated viruses.

Enteroviruses

Human enteroviral infections occur primarily via ingestion of fecally contaminated material (ie, fecal-oral route). The ingested virus replicates in susceptible tissues of the pharynx or gut. Enteroviral replication can be observed in lymphoid tissue of the small intestine within 24-72 hours of ingestion of the virus.

After multiplication in submucosal lymphatic tissues, enteroviruses pass to regional lymph nodes and give rise to a minor viremia that is transient and usually undetectable. During this low-grade viremia, the virus can spread to reticuloendothelial tissue (eg, liver, spleen, bone marrow, distant lymph nodes).

In subclinical infections, which are the most common, viral replication ceases after minor viremia because it is contained by host defense mechanisms. In a minority of infected individuals, however, further virus replication occurs in these reticuloendothelial sites, leading to major viremia. Major viremia can result in dissemination to target organs (eg, CNS, heart, skin), where necrosis and inflammatory lesions can occur. In target organs, the degree of inflammatory change and tissue necrosis corresponds to viral titer. Exercise, cold exposure, malnutrition, pregnancy, immunosuppression, and radiation can enhance the severity of the infection; enteroviral infection in persons with HIV infection may result in chronic enteroviral meningitis.

Previous
Next

Epidemiology

Frequency

United States

The overall incidence of picornavirus infections is unknown.

Most enteroviruses survive well in moist or wet environments and are readily transmitted via the fecal-oral route. Enteroviral infections occur not only in warmer climates, where they may be endemic year-round, but also with more seasonal periodicity in temperate climates (particularly during summer and fall months).[13]

Rhinoviruses have a well-established seasonal pattern that differs from those of enteroviral infections. In temperate climates, rhinoviral infections have fall and spring peaks; early-fall outbreaks of rhinoviral colds characteristically herald the respiratory disease season. In tropical areas, rhinovirus outbreaks occur during the rainy season; in the arctic, outbreaks occur during colder weather.[14]

International

Enteroviruses are distributed worldwide.[15, 16, 17, 18, 19, 20, 21]

Poliomyelitis eradication projects have typically involved mass vaccine administration with secondary emphasis on hygiene measures. By 1994, poliomyelitis was considered eradicated from the Americas. As of 2008, poliomyelitis was considered endemic in only 4 countries—Nigeria, India, Pakistan, and Afghanistan—accounting for 1392 of 1491 cases reported in 2008 (as of November 14, 2008).[18]

Mortality/Morbidity

Picornaviruses cause various illnesses. Different viruses produce different clinical pictures; in addition, a given picornavirus type can cause varying manifestations in different hosts.

HAV infection may result in fatal fulminant hepatitis. Enteroviruses, particularly enterovirus 71, may cause fatal encephalitis. Infection with coxsackieviruses may lead to nonischemic cardiomyopathy, either chronic or fulminant in nature, and has been reported to cause fatal pneumonitis.[22] Parechoviruses have been observed to cause severe, even fatal, sepsis.[23] Poliomyelitis may be fatal if respiratory support is unavailable or ineffective.

Although many picornaviral infections are asymptomatic, short-term morbidity is the rule in those that do cause symptoms.[24] Gastrointestinal and upper respiratory tract symptoms are most common. Long-term morbidity is uncommon, except for persistent neurologic deficits as a consequence of meningoencephalitis,[17, 25] chronic nonischemic cardiomyopathy, or persistent paralysis (partial or complete) or postpolio syndrome.

Race

Picornaviral infections have no known racial predilection.

Sex

The vast majority of enteroviral infections in children are asymptomatic. Some enteroviral infections, particularly those of the CNS, are more common in boys than in girls. After puberty, the reverse is true, perhaps because women have greater exposure to children who shed the virus and because of the relative immunosuppression of pregnancy.

Age

Most picornavirus infections have no age predilection, although clinical manifestations may favor certain age groups. Aseptic meningitis is most common in very young infants, whereas myocarditis and pleurodynia are most prevalent in adolescents and young adults.[26]

  • Enteroviruses: The risk of certain enterovirus-related clinical syndromes varies with age and sex. Enteroviral infections occur predominantly in children. In enteroviral infections, antibody prevalence rates of a few serotypes indicate that, after the decline of passively acquired maternal antibodies (by age 6 mo), the fraction of immune persons in the population rises progressively with age; 15%-90% of the adult population has type-specific neutralizing antibodies. Symptomatic enteroviral infections are uncommon in elderly persons. Approximately 95% of infections caused by poliovirus and at least 50% of enteroviral infections that are not associated with polio are presumed completely asymptomatic. [27]
  • Rhinovirus: Prevalence studies of rhinovirus antibody show rapid acquisition of antibody during childhood and adolescence, with peak prevalence in young adults. Colds range from 1.2 infections per year in children younger than 1 year to 0.7 infections per year in young adults. Approximately 70%-88% of rhinovirus infections are associated with symptomatic respiratory illness. [28]
Previous
 
 
Contributor Information and Disclosures
Author

Larry I Lutwick, MD Professor of Medicine, State University of New York Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus

Larry I Lutwick, MD is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Charles V Sanders, MD Edgar Hull Professor and Chairman, Department of Internal Medicine, Professor of Microbiology, Immunology and Parasitology, Louisiana State University School of Medicine at New Orleans; Medical Director, Medicine Hospital Center, Charity Hospital and Medical Center of Louisiana at New Orleans; Consulting Staff, Ochsner Medical Center

Charles V Sanders, MD is a member of the following medical societies: American College of Physicians, Alliance for the Prudent Use of Antibiotics, The Foundation for AIDS Research, Southern Society for Clinical Investigation, Southwestern Association of Clinical Microbiology, Association of Professors of Medicine, Association for Professionals in Infection Control and Epidemiology, American Clinical and Climatological Association, Infectious Disease Society for Obstetrics and Gynecology, Orleans Parish Medical Society, Southeastern Clinical Club, American Association for the Advancement of Science, Alpha Omega Alpha, American Association of University Professors, American Association for Physician Leadership, American Federation for Medical Research, American Geriatrics Society, American Lung Association, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Association of American Medical Colleges, Association of American Physicians, Infectious Diseases Society of America, Louisiana State Medical Society, Royal Society of Medicine, Sigma Xi, Society of General Internal Medicine, Southern Medical Association

Disclosure: Received royalty from Baxter International for other.

Chief Editor

Mark R Wallace, MD, FACP, FIDSA Clinical Professor of Medicine, Florida State University College of Medicine; Clinical Professor of Medicine, University of Central Florida College of Medicine

Mark R Wallace, MD, FACP, FIDSA is a member of the following medical societies: American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, International AIDS Society, Florida Infectious Diseases Society

Disclosure: Nothing to disclose.

Additional Contributors

John M Leedom, MD Professor Emeritus of Medicine, Keck School of Medicine of the University of Southern California

John M Leedom, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society for Microbiology, Infectious Diseases Society of America, International AIDS Society, Phi Beta Kappa

Disclosure: Nothing to disclose.

Acknowledgements

Yana Bron, MD Consulting Staff, Department of Pediatrics, Linden Children Services Inc

Yana Bron, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Informatics Association, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Robert L Holmes, DO Major, Medical Corps, US Air Force, Medical Director of Infectious Diseases, Chair, Infection Control Review Function, Associate Program Director, Internal Medicine Residency Training Program, Keesler Medical Center

Robert L Holmes, DO is a member of the following medical societies: American College of Physician Executives, American Osteopathic Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

References
  1. Melnick JL. Portraits of viruses: the picornaviruses. Intervirology. 1983. 20(2-3):61-100. [Medline].

  2. Atmar RL, Piedra PA, Patel SM, Greenberg SB, Couch RB, Glezen WP. Picornavirus - the Most Common Respiratory Virus Infection among Patients of All Ages Hospitalized with Acute Respiratory Illness. J Clin Microbiol. 2011 Nov 23. [Medline].

  3. Racaniello VR. Picornaviridae: the viruses and their replication. Knipe DM, Howley PM, Griffin DE. Fields Virology. 5th ed. Lippincott Williams & Wilkins; 2006. Vol 1: 795-838.

  4. Melnick JL. Properties and classification of hepatitis A virus. Vaccine. 1992. 10 Suppl 1:S24-6. [Medline].

  5. Papadopoulos NG, Sanderson G, Hunter J. Rhinoviruses replicate effectively at lower airway temperatures. J Med Virol. 1999 May. 58(1):100-4. [Medline].

  6. Jiang P, Liu Y, Ma HC, Paul AV, Wimmer E. Picornavirus Morphogenesis. Microbiol Mol Biol Rev. 2014 Sep. 78(3):418-437. [Medline].

  7. Drexler JF, Luna LK, Stöcker A, Almeida PS, Ribeiro TC, Petersen N. Circulation of 3 lineages of a novel Saffold cardiovirus in humans. Emerg Infect Dis. 2008 Sep. 14(9):1398-405. [Medline].

  8. Abraham G, Colonno RJ. Many rhinovirus serotypes share the same cellular receptor. J Virol. 1984 Aug. 51(2):340-5. [Medline].

  9. Holland J. Enterovirus entrance into specific host cells and subsequent alterations of cell protein and nucleic acid synthesis. Bacteriol Rev. 1964. 28:3-13.

  10. Lonberg-Holm K, Korant BD. Early interaction of rhinoviruses with host cells. J Virol. 1972 Jan. 9(1):29-40. [Medline].

  11. Ogram SA, Flanegan JB. Non-Templated Functions of Viral RNA in Picornavirus Replication. Curr Opin Virol. 2011 Nov 1. 1(5):339-346. [Medline]. [Full Text].

  12. Alexander HE, Koch G, Mountain IM, Sprunt K, Van Damme O. Infectivity of ribonucleic acid of poliovirus on HeLa cell mono-layers. Virology. 1958 Feb. 5(1):172-3. [Medline].

  13. Trip HF, Schonenberg D, Starreveld JS, Versteegh FG. An enterovirus epidemic in infants in the summer and fall of 2006. Eur J Clin Microbiol Infect Dis. 2008 Nov 7. [Medline].

  14. Gwaltney JM Jr. Rhinovirus. Mandell GL, Bennet JE, Dolin R. Principles and Practice of Infectious Diseases. 6th 3d. Philadelphia: Churchill Livingstone; 2005. Vol 2: 2185-94.

  15. Abed Y, Boivin G. New Saffold cardioviruses in 3 children, Canada. Emerg Infect Dis. 2008 May. 14(5):834-6. [Medline].

  16. D'Errico MM, Barbadoro P, Bacelli S, Esposto E, Moroni V, Scaccia F. Surveillance of acute flaccid paralysis in the Marches region (Italy): 1997-2007. BMC Infect Dis. 2008. 8:135. [Medline].

  17. Dos Santos GP, Skraba I, Oliveira D, Lima AA, de Melo MM, Kmetzsch CI, et al. Enterovirus meningitis in Brazil, 1998-2003. J Med Virol. 2006 Jan. 78(1):98-104. [Medline].

  18. Global Polio Eradication Initiative (partnership between World Health Organization, US Centers for Disease Control and Prevention, Rotary International, and United Nations Children's Fund). Wild Poliovirus 2000-2008. Global Polio Eradication Initiative. Available at http://www.polioeradication.org/content/general/casecount.pdf. Accessed: 21 November, 2008.

  19. Qiu J. Enterovirus 71 infection: a new threat to global public health?. Lancet Neurol. 2008 Oct. 7(10):868-9. [Medline].

  20. Tu PV, Thao NT, Perera D, Huu TK, Tien NT, Thuong TC. Epidemiologic and virologic investigation of hand, foot, and mouth disease, southern Vietnam, 2005. Emerg Infect Dis. 2007 Nov. 13(11):1733-41. [Medline].

  21. Zhao YN, Jiang QW, Jiang RJ, Chen L, Perlin DS. Echovirus 30, Jiangsu Province, China. Emerg Infect Dis. 2005 Apr. 11(4):562-7. [Medline].

  22. Legay F, Lévêque N, Gacouin A, Tattevin P, Bouet J, Thomas R. Fatal coxsackievirus A-16 pneumonitis in adult. Emerg Infect Dis. 2007 Jul. 13(7):1084-6. [Medline].

  23. Abed Y, Boivin G. Human parechovirus types 1, 2 and 3 infections in Canada. Emerg Infect Dis. 2006 Jun. 12(6):969-75. [Medline].

  24. Bell BP, Anderson DA, Feinstone SM. Hepatitis A virus. Mandell GL, Bennet JE, Dolin R. Principles and Practice of Infectious Diseases. 6th ed. Philadelphia: Churchill Livingstone; 2005. Vol 2: 2162-85.

  25. Verboon-Maciolek MA, Groenendaal F, Hahn CD, Hellmann J, van Loon AM, Boivin G, et al. Human parechovirus causes encephalitis with white matter injury in neonates. Ann Neurol. 2008 Sep. 64(3):266-73. [Medline].

  26. Chen JH, Chiu NC, Chang JH. A neonatal echovirus 11 outbreak in an obstetric clinic. J Microbiol Immunol Infect. 2005. 38:332-37. [Medline].

  27. Modlin JF. Coxsackieviruses, echoviruses, and newer enteroviruses. Mandell GL, Bennet JE, Dolin R. Principles and Practice of Infectious Diseases. 6th ed. Philadelphia: Churchill Livingstone; 2005. Vol 2: 2148-61.

  28. Makela MJ, Puhakka T, Ruuskanen O. Viruses and bacteria in the etiology of the common cold. J Clin Microbiol. 1998 Feb. 36(2):539-42. [Medline].

  29. Modlin JF. Poliovirus. Mandell GL, Bennet JE, Dolin R. Principles and Practice of Infectious Diseases. 6th ed. Philadelphia: Churchill Livingstone; 2005. Vol 2: 2141-8.

  30. Fowlkes AL, Honarmand S, Glaser C, Yagi S, Schnurr D, Oberste MS. Enterovirus-associated encephalitis in the california encephalitis project, 1998-2005. J Infect Dis. 2008 Dec 1. 198(11):1685-91. [Medline].

  31. Ding YZ, Chen HT, Zhang J, Zhou JH, Ma LN, Zhang L, et al. An overview of control strategy and diagnostic technology for foot-and-mouth disease in China. Virol J. 2013 Mar 7. 10:78. [Medline]. [Full Text].

  32. Peltola V, Waris M, Osterback R, Susi P, Hyypiä T, Ruuskanen O. Clinical effects of rhinovirus infections. J Clin Virol. 2008 Dec. 43(4):411-4. [Medline].

  33. Xiang Z, Gonzalez R, Xie Z, Xiao Y, Chen L, Li Y, et al. Human rhinovirus group C infection in children with lower respiratory tract infection. Emerg Infect Dis. 2008 Oct. 14(10):1665-7. [Medline].

  34. Andreoletti L, Blassel-Damman N, Dewilde A. Comparison of use of cerebrospinal fluid, serum, and throat swab specimens in diagnosis of enteroviral acute neurological infection by a rapid RNA detection PCR assay. J Clin Microbiol. 1998 Feb. 36(2):589-91. [Medline].

  35. Watanabe K,Oie M, Higuchi M, Nishikawa M, Fujii M. Isolation and characterizationof novel human parechovirusfrom clinical samples. Emerg Infect Dis. 2007. 13(6):889-895. [Medline].

  36. Andeweg AC, Bestebroer TM, Huybreghs M. Improved detection of rhinoviruses in clinical samples by using a newly developed nested reverse transcription-PCR assay. J Clin Microbiol. 1999 Mar. 37(3):524-30. [Medline].

  37. Molina-Ruiz AM, Santonja C, Rütten A, Cerroni L, Kutzner H, Requena L. Immunohistochemistry in the Diagnosis of Cutaneous Viral Infections- Part II: Cutaneous Viral Infections by Parvoviruses, Poxviruses, Paramyxoviridae, Picornaviridae, Retroviruses and Filoviruses. Am J Dermatopathol. 2014 Aug 28. [Medline].

  38. Feng Q, Langereis MA, van Kuppeveld FJ. Induction and suppression of innate antiviral responses by picornaviruses. Cytokine Growth Factor Rev. 2014 Jul 18. [Medline].

  39. Jaïdane H, Hober D. Role of coxsackievirus B4 in the pathogenesis of type 1 diabetes. Diabetes Metab. 2008 Oct 16. [Medline].

  40. Liang Z, Kumar AS, Jones MS, Knowles NJ, Lipton HL. Phylogenetic analysis of the species Theilovirus: emerging murine and human pathogens. J Virol. 2008 Dec. 82(23):11545-54. [Medline].

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.