Olyvia Han


The Genome ssRNA, (+) sense, linear, monopartite
The Capsid Icosahedral, naked, 30-39nm in diameter
Morphology Spherical with 32 "cupped" shaped depressions on virion

At a mere 30-40 nm in diameter this mischievous virus will wreak havoc on your gastrointestinal tract given the opportunity. Nausea, vomiting, diarrhea and abdominal cramps are prominent features in this viral infection, which lasts an undoubtedly long 1-2 days. Quite appropriately, the virus is transmitted through the fecal-oral route. However, this means that caliciviruses are highly infectious, accounting for some 40% of gastroenteritis outbreaks in the U.S. The salad you had for dinner, the partially cooked oysters they served on a recent cruise, the water young Billy drank at bedtime: all are potential routes of calicivirus transmission.

Nervous? There's more.

| Historical Notes | About the Virus | Pathogenesis & Immunity |
| Prevention | Update | Researchers of the Day | Useful Web Links | References |

+A Little History

Caliciviruses were well known to veterinary virologist by the time the first documented human calicivirus erupted in Norwalk, Ohio in 1969. Within a mere 48 hours half of the students and teachers at a local elementary school had been stricken with gastroenteritis. Secondary transmission infected nearly a third of familial contacts thereafter. A bacteria-free filtrate from a stool specimen was analyzed but no agent was isolated in the usual cell culture systems. It was nearly three years later that the structure of the so-called "Norwalk" virus was elucidated via immune electron microscopy by Kapikian et al. A small, 27-nm-diameter RNA virus was eventually isolated. Norwalk and the Norwalk-like viruses that followed it were initially lumped under the family picornaviridae given their small size and spherical morphology. They differed in their strategy for genomic replication, however, and where picornaviruses had 4 capsid proteins these viruses only had one. Ultimately, gene sequencing proved these viruses to be members of the family caliciviridae.

+ About the Virus

Calicivirus replication occurs in the cytoplasm. The 7.5-7.7 kb plus sense linear ssRNA genome has a VPg protein covalently attached to its 5' terminus (except in hepatitis E which is capped instead) and a polyadenylated tail. There are three open reading frames, the longest of which encodes non-structural proteins that include an RNA-dependent polymerase, ATPase/helicase, and a protease. Post-translational processing yields the final protein product. It appears that a nested set of 3' subgenomic transcripts code for the remaining proteins, most notable of which is the capsid protein.

+ Pathogenesis & Immunity

In Norwalk viral gastroenteritis the tips of the villi in the intestinal jejunum slough off. There is infiltration of mononuclear cells and polymorphs, but the gastric mucosa remains histologically intact. Transient malabsorbtion and delayed gastric emptying soon follow. The illness usually runs its course in about 1-2 days. Acquired immunity is poor, lasting a year or so at best.

+ Prevention

Prevention requires a concerted effort to improve sanitation and hygiene standards within any community. Thus many outbreaks can be prevented by enforcing sanitation standards that apply to the preparation and supply of food for public consumption, for many epidemics start at the hands of an ill food handler.

Interestingly, however, nearly half of all the Norwalk outbreaks investigated by the Center for Disease Control have been traced back to shellfish that was served raw or undercooked. Shellfish are notorious for concentrating viruses in fecally contaminated waters. Thorough cooking of food is a very good means of preventing viral transmission. Unfortunately, uncooked foods such as salads thus pose the greatest risk.

Interestingly enough, caliciviruses are also relatively resistant to chlorination of water. Standard water chlorination levels hover between .2-5 mg/Liter, concentrations which are adequate to destroy most bacteria and viruses. The Norwalk virus can survive at concentrations below 10 mg/Liter.

+An Update

Recently molecular techniques have developed for detection and diagnosis of enteric viruses in water samples. This has proved to be a boon to Public Health officials who are concerned about the transmission of Norwalk through shellfish consumption and contaminated water resources. The techniqe now known as reverse transcriptase-polymerase chain reaction is being refined, and problems of interference and sensitivity are being addressed.

On a different note, a recent study published by J.M. Ball and M.E Hardy in Journal of Virologyrevealed that non-replicating recombinant Norwalk virus-like particles, or, rNV VLPs have been found to induce an immune response when administered orally - even in the absence of delivery system or mucosal adjuvant. rNV VLPs have thus been found to be an excellent model to study the oral delivery of antigen, but more importantly to this discussion, they may prove to be a potential mucosal vaccine for NV infections.

+ Researchers of the Day

+ Albert Kapikian - Using electron micrograph techniques Kapikian elucidated the structure of the calicivirus capsid. Kapikian also studied the molecular differences between Hawaii virus and other Norwalk-like viruses.

+ J. Redman - Redman studied the relationship between electrostatic viral properties and filtering media to determine what governs the physicochemical filtration of the virus. In his studies, Redman utilized the bacteriophage MS2 as a model of typical waterborne viral pathogens.

+ Robert Atmar - Atmar helped to develop a new PCR-based technique to detect both Norwalk virus and Hepatitis A virus in shellfish. His method also possessed internal standards for quantifying the level of viral RNA present in a sample. The assay was tested on oysters and hard-shell clams and was found to be faster and more sensitive than an earlier method.

+ Useful Web Links

- The Norwalk Virus Infection -
- All the Virology on the WWW -
- Morbidity and Mortality Weekly Report -
- Emily Chen's Calicivirus Page -

+ References

+ White and Fenner Medical Virology Academic Press: San Diego 1994 (407-412)

+ Ginsberg and Dulbecco Virology J.B. Lippincott Co.: Philadelphia 1988 (318-319)

+ Joklik, W. Virology Appleton-Century-Crofts: Conneticut 1985 (236-237)

+ Electron micrographs courtesy of ICTV and the Wadsworth Center of the New York State Dept. of Health

+ "The use of reverse transcriptase-polymerase chain reaction to investigate environmental samples for the presence of enteroviruses" Commun Dis Public Health 1998 Mar, 1(1):58-60.

+ "Oral Immunization with recombinant Norwalk virus-like particles induces a systemic and mucosal immune response in mice" Ball, JM; Hardy, ME; Atmar, RL; Conner, ME; Estes, MK. Oral immunization Journal of Virology 1998 Feb 72(2):1345-53.

+"Molecular characterization of Hawaii virus and other norwalk-like viruses: Evidence for genetic polymorphism among human caliciviruses" Lew, J.; Kapikian, A. ; Valdesuso, J.; Journal of Infectious Diseases; 1994; v.170, no.3, p.535-542.

+ Redman, J. A.; Grant, S. B.; Olson, T. M. "Filtration of recombinant Norwalk virus particles and bacteriophage MS2 in quartz sand: importance of electrostatic interactions" Environmental Science & Technology v31, n12 (Dec, 1997):3378

+ Atmar, Robert L.; Neill, Frederick H.; Romalde, Jesus L.; Le Guyader, Francoise; Woodley, Cheryl M.; Metcalf, Theodore G.; Estes, Mary K. "Detection of Norwalk virus and hepatitis A virus in shellfish tissues with the PCR.(polymerase chain reaction)" Applied and Environmental Microbiology v61, n8 (August, 1995):3014


Humans and Viruses
Human Biology 115A
Winter, 1999
Robert Siegel, instructor
Created: February 1, 1999
Last modified: February 1, 1999