Picornaviruses

 Viruses with Single-Stranded RNA Genomes, Sense-Strand Orientation

The important human pathogenic genera of picornaviruses are:

-Enteroviruses with the polioviruses (poliomyelitis), cocksackieviruses and echoviruses.

-Parechoviruses types 1 and type 2.

-Hepatoviruses with the hepatitis A virus.

-Rhinoviruses, common cold viruses (rhinitis).

Transmission of enteroviruses, parechoviruses, and hepatoviruses is by the fecal-oral route. The viruses first replicate in the intestine, from which location they reach their target organ with the bloodstream. Large numbers of inapparent infections are typical of this group.

Rhinoviruses are transmitted by droplet infection and remain restricted to the upper respiratory mucosa.

Diagnosis: enteroviruses and parechoviruses are diagnosed by isolation in cell cultures or with PCR, hepatitis A serologically (IgM) and rhinoviruses, if at all, by isolation.

Prevention: basic polio immunization with dead or live vaccine; hepatitis A with dead vaccine; exposure prophylaxis with rhinoviruses.  

The picornaviruses (Fig. 1: polioviruses) are among the most thor­oughly studied viruses of all. The name picorna is an abbreviation that stands for two characteristics of this family: they are small (pico) viruses with an RNA genome (rna). The RNA is polyadenylated at its 3' end and has no cap at the 5' end, but instead a virus-coded, basic protein about 2 kDa in size, the VPg  (virus protein, genome-linked). It consists of approximately

Fig. 1 Polioviruses are 24–30 nm in size and cause poliomyelitis.

7500 bases forming 2207 coding triplets (in the poliovirus). The combination of the ribo­somes with the RNA is not, as in cellular mRNA, at the cap of the 5' end (“scan­ning model”) but rather internally in the nontranslated region (NTR), which is about 750 nucleotides long and is positioned before the coding segment. The translation product of this RNA is a precursor polyprotein about 250 kDa in size, which is proteolytically divided into about 20 individual, functional pro­teins during or immediately after its synthesis. The N-terminal end of the polyprotein contains the capsid proteins, the middle region proteins that con­tribute to the expression of the structures required for RNA replication and formation of the CPE  and the C-terminal segment includes proteins of an enzymatic character (protease for proteolytic cleavage of the primary translation product, see above, and the RNA-dependent RNA polymerase) as well as VPg, which functions as a primer for RNA synthesis.

The different human pathogenic genera of picornaviruses are the ente­roviruses, parechoviruses, hepatoviruses, and rhinoviruses.

Enteroviruses (Poliovirus, Coxsackievirus, Echovirus) and Parechoviruses

Pathogen. The genus Enterovirus, isolated from the intestinal tract, includes these species:

-Poliovirus (poliomyelitis pathogen) with three serotypes.

-Coxsackievirus, group A, with 22 serotypes.

-Coxsackievirus, group B, with six serotypes.

-Echovirus with 34 serotypes.

-Enteroviruses numbers 68-71.

The genus Parechovirus includes the species parechovirus types 1 and 2.

Pathogenesis and clinical pictures. The enteroviruses and parechoviruses are transmitted per os and replicate at first in the lymphoid tissue of the pha­ryngeal space, later mainly in the intestinal wall. They then reach their “target organs” via the bloodstream (e.g., CNS, muscles, heart, liver), followed by manifest organ infection, which, however, only develops in a small percen­tage of cases. Most infections run an asymptomatic course. Viremia is always present, so that even asymptomatic enterovirus and parechovirus infections confer effective immunity. The cases of manifest infection frequently run atypical courses with mild clinical symptoms. The same viral type can cause different symptoms and several different viral types can cause a given clinical symptom. Recently, severe complications have been described, mainly as a sequel to hand, foot, and mouth disease (HFMD, Table 1) in Southeast Asia.

The following clinical pictures have been described for enteroviruses and parechoviruses (Table 1):

Diagnosis. The available laboratory diagnostic tools include PCR or isolation of the virus from cerebrospinal fluid, pharyngeal smear, or lavage, with the best chances of success from stool. Serodiagnosis plays only a minor role.

Epidemiology and prevention. Humans are the reservoir of the entero­viruses. Transmission is either direct (smear infection) or in food and water.

Table 1 Enteroviruses and Parechoviruses: Clinical Syndromes

Where hygienic standards are high, droplet infections also play a significant role. Special prophylactic measures to prevent infections with coxsackie­viruses or echoviruses are neither practicable nor generally necessary.

Salk introduced a dead vaccine in 1954 for poliomyelitis prophylaxis (IPV, inactivated polio vaccine) consisting of three poliovirus types inactivated by formalin. Five years later, the live vaccine (OPV, oral polio vaccine according to Sabin) was introduced, which contains three live but no longer neurovirulent poliovirus strains, either singly or in combination. The WHO plan to eradicate poliomyelitis worldwide would seem feasible with this vaccine as demon­strated by its eradication in several countries including all of South America.

Hepatoviruses (Hepatitis A Virus)

Pathogen. The hepatitis A virus differs in some characteristics from entero­viruses, to which group it was long considered to belong. Growth in cell cul­tures requires long adaptation. Only one serotype is known to date.

Pathogenesis and clinical picture. The clinical picture of hepatitis A, so- called epidemic or infectious hepatitis, differs in no major particulars from that of hepatitis B. The disease nearly always takes a benign course. Only a small number of fulminant (and sometimes lethal) or chronic courses have been described. The pathogenic process at first corresponds to that of the enteroviruses, whereby hepatitis A replicates in the intestine and then, after a brief viremic episode, attacks its target organ, the liver. Disease man­ifestation with this pathogen, unlike most of the enteroviruses but similar to hepatitis B, involves immunological processes.

Diagnosis is based on IgM detection due to the early presence of these anti­bodies in patient serum, in fact so early that a lack of hepatitis A antibodies at the onset of clinical manifestations excludes hepatitis A.

Epidemiology and prevention. Transmission is by food and water or in the form of smear infections. Infection with hepatitis A shows a clear north-south gradient: it has become virtually a travelers' disease in central Europe. Im­ported cases frequently cause minor outbreaks in families or schools. Active immunization with an inactivated HAV vaccine is available.

Rhinoviruses

Pathogens. The genomic organization and replication system of the rhino- viruses (117 serotypes found to date) generally match those of the entero­viruses, although they differ in that they are acid-sensitive and slightly denser.

Pathogenicity and clinical picture. The rhinoviruses, the causative pathogens of the common cold, infect the mucosa of the nasopharyngeal space (nose and throat). They remain strictly localized there and do not cause generalized infections. In rare cases, mainly in children, they are known to cause bron­chitis or bronchopneumonia as well. The clinical picture is often worsened by bacterial superinfection.

Diagnosis. Laboratory diagnostics are only required in special cases of rhino- virus infection. The viruses can be grown in cell cultures.

Epidemiology and prevention. Rhinoviruses are transmitted directly, for example by contaminated hands, and partly by droplet infection as well. In­fective contacts between humans appear to involve mechanical inoculation (introduction into the nasopharyngeal space with fingers). Rhinoviruses occur worldwide, with pronounced proliferation in the winter months. The fact that everyone comes down with colds repeatedly is explained by the very brief immunity conferred by infection and the many different viral types involved. Experiments have shown that the infections are always exogenous, i.e., not reactivations due to cold, wetness, etc. The only conceiv­able prophylactic measure is to avoid large groups of people.