Picornaviridae

Subjects: virology, microbiology · Systems: virology, microbiology · Tags: virology, microbiology

Picornaviridae

Picornaviruses are small, non-enveloped, icosahedral viruses with a positive-sense, single-stranded RNA genome of roughly 7–8.5 kb. Their name—“pico” for small and “RNA”—captures two defining features: a compact particle of about 30 nm and an RNA genome that functions directly as mRNA. The 5′ end of the genome is covalently linked to a small viral protein (VPg) rather than a eukaryotic cap, and the 3′ end carries a poly(A) tail. Translation is cap-independent via a highly structured internal ribosome entry site (IRES) in the 5′ untranslated region; poliovirus, coxsackievirus, echovirus, and rhinovirus use type I IRES elements, whereas hepatitis A virus (HAV) uses a distinct type III IRES. The entire genome is translated as a single polyprotein that is co- and post-translationally cleaved by virally encoded proteases (notably 2A and 3C) into structural proteins (VP1–VP4, derived from the P1 region) and nonstructural proteins (from P2 and P3) that drive replication. Replication is entirely cytoplasmic: the RNA-dependent RNA polymerase 3Dpol synthesizes a negative-strand template and then copies it into new positive strands within membrane-bound replication organelles remodeled from the endoplasmic reticulum and Golgi by viral proteins 2B, 2C, and 3A.

Although the family is large, three human genera dominate medical examinations. Enteroviruses include poliovirus, coxsackie A and B viruses, echoviruses, and newer numbered types such as enterovirus D68 and A71. Rhinoviruses, despite their name, are also enteroviruses taxonomically but are classically treated apart clinically as the major cause of the common cold. Hepatoviruses are represented in humans by HAV. Other human picornaviruses—parechoviruses and kobuviruses—are encountered less often but matter in pediatrics and outbreaks. Acid stability and growth temperature help segregate clinical niches: enteroviruses are acid stable and survive gastric transit, enabling fecal–oral spread; rhinoviruses are acid labile and prefer cooler temperatures around 33 °C, favoring the upper respiratory tract; HAV is acid stable and environmentally hardy, supporting transmission via contaminated food and water.

Cell entry and tropism hinge on receptor usage and post-entry events. Poliovirus binds CD155 (the poliovirus receptor, PVR); many coxsackie and echoviruses use the coxsackie-adenovirus receptor (CAR) or decay-accelerating factor (DAF); rhinoviruses in the “major group” attach to ICAM-1 on nasal epithelial cells, with a “minor group” using LDL receptor family members; enterovirus A71 can use SCARB2 and PSGL-1; enterovirus D68 interacts with sialylated glycans in the airways; HAV binds TIM-1 (HAVcr-1) and circulates in blood cloaked as a quasi-enveloped particle within host-derived membranes, only shedding as a naked, bile-resistant virion into stool. Once internalized, picornaviruses rapidly subvert host translation: the 2A protease cleaves eIF4G and halts cap-dependent host protein synthesis, while the viral IRES continues to recruit ribosomes to viral RNA. The 3C protease and other nonstructural proteins also antagonize innate immunity by targeting RIG-I/MDA5 signaling adaptors (such as MAVS and TRIF), interfering with interferon induction and signaling. The RNA polymerase lacks proofreading, generating quasispecies and enabling immune escape and, in the case of poliovirus and EV-A71, the emergence of neurovirulent variants.

Enteroviruses present with a broad clinical spectrum that reflects viremic dissemination after initial replication in the oropharynx and gut. Poliovirus is the archetype: most infections are asymptomatic or cause a minor febrile illness; a subset develops aseptic meningitis; and fewer still develop paralytic poliomyelitis when virus targets anterior horn motor neurons, producing acute, asymmetric flaccid paralysis with hyporeflexia and no sensory loss. Coxsackie A viruses are classically linked to herpangina—painful vesicles on the soft palate—and to hand-foot-and-mouth disease, in which oral ulcers accompany vesicular lesions on palms and soles; enterovirus A71 is notable because it can complicate HFMD with brainstem encephalitis and neurogenic pulmonary edema. Coxsackie B viruses show tropism for muscle and myocardium, causing pleurodynia (Bornholm disease) with sharp chest pain and fever, as well as myocarditis and pericarditis; they are also implicated in neonatal sepsis-like syndromes acquired peripartum. Echoviruses and other non-polio enteroviruses are leading causes of aseptic meningitis, especially in summer and early fall. Enterovirus D68 occupies a respiratory niche with wheezing illnesses in children and has been temporally associated with clusters of acute flaccid myelitis characterized by spinal gray matter lesions and focal limb weakness. Epidemic acute hemorrhagic conjunctivitis has been linked to enterovirus 70 and coxsackie A24 variant, producing abrupt, painful, subconjunctival hemorrhages in explosive outbreaks. In agammaglobulinemic patients, enteroviruses can produce chronic meningoencephalitis because neutralizing antibody is essential for clearance.

Rhinovirus is the pre-eminent cause of the common cold, with hundreds of antigenically distinct types that frustrate vaccine development. Illness begins after a short incubation with nasal congestion, rhinorrhea, sore throat, and cough, generally without fever in adults. Disease reflects cytokine-driven inflammation rather than frank cytolysis, and viral replication at cooler nasal temperatures helps explain the upper-airway confinement. Nonetheless, rhinovirus is a major trigger of asthma and COPD exacerbations, and it readily spreads via respiratory droplets and fomites owing to its environmental resilience as a non-enveloped virus.

Hepatitis A virus illustrates how a picornavirus can cause systemic disease without chronicity. After ingestion, HAV replicates in the gut and spreads hematogenously to the liver, where it infects hepatocytes but causes injury largely through the host immune response rather than direct cytopathic effect. The incubation averages four weeks, followed by a prodrome of fever, malaise, anorexia, nausea, and right upper quadrant discomfort; dark urine and jaundice then appear, most reliably in adults. Children often have anicteric disease, facilitating silent spread. Viremia and fecal shedding peak before jaundice, which is why patients are most infectious before they feel ill. Fulminant hepatic failure is uncommon but can occur, particularly in older adults or those with underlying liver disease. Importantly, HAV does not establish chronic infection, although prolonged cholestatic or relapsing courses are recognized. The virus is shed in enormous quantities and resists many environmental conditions; improved sanitation and highly effective inactivated vaccines have transformed its epidemiology, with outbreaks now concentrated among unvaccinated communities, travelers to endemic regions, people who use drugs, and men who have sex with men.

Human parechoviruses, historically grouped with enteroviruses, deserve a brief note because type 3 can cause severe neonatal disease with sepsis-like presentations and meningoencephalitis. A striking feature in these infants is a paucity of cerebrospinal fluid pleocytosis despite high viral loads, which can mislead clinicians unless PCR testing is performed. Kobuviruses such as Aichi virus have been associated with gastroenteritis outbreaks linked to contaminated food, though their role is less prominent than caliciviruses.

Diagnosis across the family depends on the syndrome and the virus. For suspected enteroviral meningitis, polymerase chain reaction on cerebrospinal fluid is the test of choice and has largely supplanted culture. Respiratory infections attributed to rhinovirus or enteroviruses are identified by multiplex nucleic-acid panels on nasopharyngeal swabs. Suspected poliomyelitis prompts stool and nasopharyngeal sampling for poliovirus detection and typing, with magnetic resonance imaging of the spinal cord revealing T2 hyperintensity in the anterior horns in paralytic cases. Acute flaccid myelitis evaluations increasingly include enterovirus D68 PCR from respiratory samples and sequencing for surveillance. Hepatitis A is diagnosed serologically by anti-HAV IgM in the appropriate clinical context, with IgG indicating past infection or vaccine-induced immunity. In neonatal or immunocompromised enteroviral disease, plasma PCR can be helpful because viremia may be sustained.

Treatment is predominantly supportive. Most non-polio enteroviral and rhinoviral infections resolve without specific therapy; bronchodilators and supportive respiratory care address lower-tract disease when present. IVIG can be beneficial in severe neonatal enterovirus infection and in chronic enteroviral meningoencephalitis of patients with humoral immunodeficiency, reflecting the importance of neutralizing antibodies. Antiviral agents that target the picornaviral capsid (such as pleconaril or newer capsid binders) have shown activity in vitro and in limited clinical settings but are not in routine clinical use. Hepatitis A therapy is supportive as well, with attention to hydration and avoidance of hepatotoxins; post-exposure prophylaxis with inactivated HAV vaccine, immune globulin, or both—depending on age and risk—prevents disease when administered promptly after exposure. Prevention otherwise relies on hygiene and environmental control measures that take into account the robustness of non-enveloped viruses; alcohol-based hand rubs are less reliable against some picornaviruses than chlorine-containing disinfectants and thorough handwashing with soap and water.

Vaccination reshaped two corners of picornavirus medicine. Global polio eradication efforts rely on inactivated poliovirus vaccine (IPV) and, in certain programs, live oral poliovirus vaccine (OPV). IPV is safe and induces excellent humoral immunity but confers less intestinal mucosal immunity; OPV induces mucosal immunity and interrupts transmission but rarely reverts to neurovirulence, causing vaccine-associated paralytic poliomyelitis or circulating vaccine-derived poliovirus in under-immunized populations. Hepatitis A vaccination, administered in early childhood or to at-risk adults, produces durable protective immunity and has driven striking declines in hospitalization and mortality. In contrast, rhinovirus vaccination remains elusive due to antigenic diversity and the limited severity of typical illness.

A few principles integrate the family for exam purposes. Picornaviruses translate via IRES and shut down host cap-dependent translation, allowing viral protein synthesis to proceed while the cell’s own synthesis stalls. Acid stability predicts the transmission route: enteric picornaviruses survive the stomach and spread fecal–orally; rhinoviruses do not and therefore spread by droplets and contact. Clinical tropism reflects receptor use and post-entry constraints: anterior horn neuron infection is the sine qua non of paralytic polio; myocarditis signals coxsackie B; vesicles on hands, feet, and mouth point to coxsackie A and enterovirus A71; wheeze clusters with enterovirus D68 in late summer; and abrupt, self-limited hepatitis with fecal–oral exposures signals HAV. The absence of a viral polymerase proofreading function sustains rapid evolution, demanding vaccination for control where possible and vigilance where not.

Disclaimer: For education only. Not medical advice; always follow your institution's guidance.