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 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.
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.
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.
- The Norwalk
Virus Infection -
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
Prevention
An
Update
Researchers of
the Day
- All the
Virology
on the WWW -
- Morbidity and
Mortality Weekly Report -
- Emily
Chen's Calicivirus Page -
References
Humans and Viruses
Human Biology 115A
Winter, 1999
Robert Siegel, instructor
Created: February 1, 1999
Last modified: February 1, 1999