PICORNAVIRUSES

The genome RNA is unusual because it has a protein on the 5′ end that serves as a primer for transcription by RNA polymerase. Picornaviruses replicate in the cytoplasm of cells. The picornavirus includes two groups of medical importance: the enteroviruses and the rhinoviruses.

ENTEROVIRUSES

Enteroviruses infect primarily the enteric tract. Enteroviruses replicate optimally at 37°C. Enteroviruses are stable under acid conditions (pH 3–5), which enables them to survive exposure to gastric acid

Poliovirus

Characteristics—Genome RNA acts as mRNA and is translated into one large polypeptide, which is cleaved by virus– encoded protease to form functional viral proteins.

Summary of Replicative Cycle

• The virion interacts with specific cell receptors on the cell membrane and then enters the cell.
• After uncoating, the genome RNA functions as mRNA and is translated into one very large polypeptide called noncapsid viral protein 00.
• This polypeptide is cleaved by a virus-encoded protease in multiple steps to form both the capsid proteins of the progeny virions and several noncapsid proteins, including the RNA polymerase that synthesizes the progeny RNA genomes.
• Replication of the genome occurs by synthesis of a complementary negative strand, which then serves as the template for the positive strands.
• Some of these positive strands function as mRNA to make more viral proteins, and the remainder become progeny virion genome RNA.
• Assembly of the progeny virions occurs by coating of the genome RNA with capsid proteins.
• Virions accumulate in the cell cytoplasm and are released upon death of the cell. They do not bud from the cell membrane.

Pathogenesis—The virus replicates in the pharynx and the GI tract. It can spread to the local lymph nodes and then through the bloodstream to the central nervous system. Most infections are asymptomatic or very mild. Aseptic meningitis is more frequent than paralytic polio. Paralysis is the result of death of motor neurons, especially anterior horn cells in the spinal cord. Pathogenesis of postpolio syndrome is unknown.

 Coxsackie Viruses

Summary of Replicative Cycle – Replication is similar to that of poliovirus.

Pathogenesis—The initial site of infection is the oropharynx, but the main site is the GI tract. The virus spreads through the bloodstream to various organs.

Hand, foot and mouth disease	Herpangina
Coxsackie A16	Coxsackie A1-6, 8, 10, 22
Airborne, feco-oral	Feco-oral, contaminated saliva
Children	Children
Fever, malaise, lymphadenopathy, sore mouth	Fever, malaise, dysphagia, sore throat
Oral vesicles – yellow membrane and erythematous halo, also on hand and foot	Vesicles ulcerate in soft palate and pharynx
Resolution in 1-2 weeks, symptomatic treatment	Self limiting

RHINOVIRUSES

Characteristics— Rhinoviruses are found in the nose and throat. Rhinoviruses grow at 33°c, in accordance with the lower temperature of the nose. Rhinoviruses are destroyed by stomach acid and therefore do not replicate in the GI tract.

Summary of Replicative Cycle- Replication is similar to that of poliovirus. The cell surface receptor for rhinoviruses is intracellular adhesion molecule 1 (ICAM-1)

Pathogenesis—Infection is limited to the mucosa of the upper respiratory tract and conjunctiva. The virus replicates best at the low temperatures of the nose and less well at 37°C, which explains its failure to infect the lower respiratory tract.

 CALICIVIRUSES

Norwalk Virus (Norovirus)

Pathogenesis—Infection is typically limited to the mucosal cells of the intestinal tract. Watery diarrhea without red cells or white cells occurs. Many infections are asymptomatic. Immunity is brief and reinfection occurs.

REOVIRUSES

Rotavirus

Characteristics— Rotavirus is resistant to stomach acid and hence can reach the small intestine. There are at least six serotypes.

Summary of Replicative Cycle

• Rotavirus attaches to the cell surface at the site of the β-adrenergic receptor.
• After entry of the virion into the cell, the RNA-dependent RNA polymerase synthesizes mRNA from each of the 11 segments within the cytoplasm.
• The 11 mRNAs are translated into the corresponding number of structural and nonstructural proteins.
• One of these, an RNA polymerase, synthesizes minus strands that will become part of the genome of the progeny virus.
• Capsid proteins form an incomplete capsid around the minus strands, and then the plus strands of the progeny genome segments are synthesized.
• The virus is released from the cytoplasm by lysis of the cell, not by budding.

Pathogenesis— Rotavirus replicates in the mucosal cells of the small intestine, resulting in the excess secretion of fluids and electrolytes into the bowel lumen. The consequent loss of salt, glucose, and water leads to diarrhea. Diarrhea is nonbloody.