Caliciviridae Infections

5 things to remember about Pathogen Name:

1. Human Caliciviruses cause worldwide outbreaks of gastroenteritis 

2. Poor Hygiene and wastewater spills are usually responsible for outbreaks

3. Human caliciviruses are not easily detected in water or the environment

4. Not grown in cell or animal cultures

5. Methods for detection are radically changing our perception of this pathogen.

Current Calicivirus research areas (relevant to Environmental Engineering):

1. Methods for culturing

2. Sensitive, simple detection methods

3. Vaccine using virus like particles (VLP’s)

4. Investigation of whether animal to human transmission is possible

5. Suitable indicator organisms

Classification

Since the discovery of Norwalk Virus in 1972, there has been much confusion and debate concerning the classification of Human Caliciviruses.  The development of a meaningful classification scheme has been hindered by a lack of effective detection methods.   A major breakthrough, the cloning of the Norwalk Virus (NV) genome in 1990, led to the classification of NV and other related small round structured viruses (SRSV’s) as members of the Family Calicirividae.  In 1998 the International Committee of Taxonomy of Viruses (ICTV) accepted the division of Caliciviridae into four new genera, two of which include those viruses that are know to infect humans.

Caliciviruses are typically 27-40 nm in diameter.  They are composed of a positive strands of ssRNA and are non-enveloped and icosohedral.  The virions are composed of a single major capsid protein.  The name calicivirus is derived from the Latin calyx, meaning cup or goblet, and refers to the cup-shaped depressions in certain strains.

Disease (Symptoms and Treatment)

In the absence of an animal model, human volunteers became the sole means to examine questions of natural immunity, pathogenesis, and the effects of treatments to inactivate the virus.

Infection with Human Caliciviruses may cause acute gastroenteritis, inflammation of the stomach and small and large intestines.  Symptoms include vomiting, primarily in children, and diarrhea, primarily in adults.  Most infections are self-limiting and do not require medical attention, however, children and persons with compromised immunity may need hospitalization for dehydration.

Oral rehydration therapy is the recommended treatment prescribed to avoid severe dehydration.

Transmission Routes and Life Cycle

The primary transmission route is via the Fecal-Oral route.  Most outbreaks of Human Caliciviruses are attributed to food and water.  Many outbreaks have been linked to poor hygiene in food handlers and infected oysters. 

The life cycle is assumed to be similar to all ssRNA viral particles.  The infectious cycle begins by attachment by the virus to the host cell; this step is followed by penetration and uncoating of the RNA.  SsRNA in the host cell serve as mRNA in the translation of proteins and function as a template for genome synthesis.   Viral DNA and the capsid proteins then self assemble into new virus particles, which leave the cell.

Little is known about the replication site of Human Caliciviruses, but we assume they replicate in the upper intestinal tract.  There is a broadening and blunting of the villi of the proximal small intestine though the mucosa remains intact.  It is suspected that a delay in gastric emptying is responsible for nausea in infected individuals.

Occurrence and Affected Population

Human Caliciviruses affect people in both developed and developing countries worldwide.  People in developed countries show a seroprevelance ranging from 50-70%.  Seroprevelence rates are higher in developing countries and studies have shown that children develop antibodies at an earlier age.

Detection Methods

Knowledge of Calicivirus has been seriously limited by less than ideal detection methods.  Initially, electron microscopy (EM) was used to detect the virus, but diagnosis using this technique is challenging for a variety of reasons.   At least 10^6 viral particles are necessary for detection in stool specimens and it requires highly skilled microscopists and expensive equipment.   Immuno-electron microscopy (IEM) was developed by shortly after the discovery of the Norwalk virus.  This technique uses immune serum to aid in virus identification but suffers from the same shortcomings as EM.  In 1978, a radio-immunoassay (RIA) was introduced for serologic testing.  RIA antigen and antibody detections assays were used to further characterize infection and illness in human volunteer studies, to perform seroprevalence studies, and to investigate outbreaks of gastroenteritis. In 1995, reverse transcriptase polymerase chain reaction (RT-PCR) was introduced, and has since become the laboratory standard.

Inactivation and Survival in the Environment

Until recently, inactivation studies have been limited to studies employing volunteers.  Caliciviruses remain infective to volunteers following:  pH 2.7, 20% ether at 4 degrees C for 18 hours, 60 degree temperatures for 30 minutes, and chlorine levels consistent with those found in drinking water systems.

Nothing is known about the survival of Caliciviruses in the environment, as they are not easily detectable in food or water samples.