PICORNAVIRIDAE virus and mode of transmission.pptx

Pacoviridea viruses

1. PICORNAVIRIDAE

2. QUESTIONS What are the structural and genomic characteristics of Picornaviridae, and how do these features enable Enteroviruses, Rhinoviruses and Hepatitis A virus to survive and replicate in different environments within the human body? Discuss the pathogenesis and clinical manifestations of infections caused by Enteroviruses particularly Polioviruses, Coxsackie A and B viruses and Echoviruses. How do these viruses contribute to diseases such as poliomyelitis ,hand-foot-mouth disease and myocarditis? Explain the role of Rhinoviruses in causing the common cold. What are the key factors that influence the high prevalence and rapid transmission of Rhinovirus infections, especially in upper respiratory infections?

3. INTRODUCTION Picornaviruses The name “picorna” is derived from pico (small), + RNA -containing. They include two major groups of human pathogens: enteroviruses and rhinoviruses . Enteroviruses are transient inhabitants of the human alimentary tract and may be isolated from the throat or lower intestine . Rhinoviruses are associated with the respiratory tract and isolated chiefly from the nose and throat . Picornaviridae contains the following genera; Enterovirus, Hepatovirus , Kobuvirus , Parechovirus , Cardiovirus , Apthovirus

4. STRUCTURAL AND GENOMIC CHARACTERISTICS OF PICORNAVIRIDAE Virion : Icosahedral, 28–30 nm in diameter, contains 60 subunits. These are the smallest (28 nm in diameter) RNA viruses. Composition: They have single-stranded, linear, nonsegmented, positive-polarity RNA within a naked icosahedral capsid Proteins : Four major polypeptides cleaved from a large precursor polyprotein . Surface capsid proteins VP1 and VP3 are major antibody-binding sites. VP4 is an internal protein. Envelope: None Genome: Single-stranded RNA, linear, positive sense, 7.2–8.4 kb in size , molecular weight 2.5 million, infectious, contains genome linked protein (VPg ). G enome is polyadenylated at the 3′ end and has a small viral-coded protein (VPg) covalently bound to the 5′ end. The positive-sense genomic RNA is infectious.

5. ENTEROVIRUSES, RHINOVIRUSES AND HEPATITIS A REPLICATION Enterovirus replication Virus binds to cell receptor via FcRn and DAF/CD55 receptors The virion forms a pore on host cell, virion protein is removed, RNA released in cytoplasm and the viral RNA is translated. The polyprotein is cleaved to produce distinct viral proteins Viral RNA polymerase copied to produce negative sense RNA strand The negative sense RNA strands are ultimately copied to produce more positive sensed RNA strands, which act as templet for translation of viral proteins. Viral protein can be enclosed in capsid which generates virions . In later infection, the positive sense RNA strands enter morphogenetic pathway Cell lysis occurs releasing newly synthesized virus particles

6. Adaptation to Different Environments Enteroviruses Members: Polioviruses, Coxsackieviruses, Echoviruses Acid Stability: Capsid proteins confer resistance to stomach acid Transmission: Fecal-oral route Replication: Survive GI tract, replicate in intestines Positive-sense RNA allows immediate protein synthesis Systemic Spread: NTR aids in efficient protein production and dissemination via bloodstream Inapparent Infections: High rate contributes to widespread transmission

7. PATHOGENESIS OF ENTERO VIRUSES These viruses are ingested and infect cells of GI tract. If the infection remains in the GI tract, it is asymptomatic. Yet, life-long immunity is acquired. Pathogenesis depends on the stability of viruses over a wide pH range (pH 3-9) and the systemic spread of virus through lymph and blood.

8. POLIOVIRUSES Serotypes of Poliovirus Poliovirus-1 Poliovirus-2 Poliovirus-3

9. POLIOVIRUSES PATHOGENESIS The incubation period is usually 7 - 14 days. Following ingestion, the virus multiplies in the oropharyngeal and intestinal mucosa. Binds to polio virus-immunoglobulin like receptor CD155 on cells. Primary Replication: Then virus hijacks the hosts cell own machinery and begins to replicate. Over 1 week: it spreads to follicular dendritic cells on tonsils.

10. CONTN……. Then invades lymphatic system, deep cervical and mesenteric lymph nodes and M cells of Peyer's patches of the ileum, Dissemination: Later virus enters the blood resulting in a transient viremia . The virus invades the CNS meninges and multiplies abundantly. Replicates along nerve fiber pathway. In spinal cord, brain stem and motor cortex. D estroys of neuronal cells and produce lesions within vestibular nuclei, celebellar vermis & nuclei and spinal ganglia. Inflammation in grey matter is associated with nerve cell destruction. Destructive changes in forebrain, hypothalamus and thalamus-affects breathing; bulbar poliomyelitis Infects anterior horn cells of motor neurons in spinal cord causing flaccid paralysis (poliomyelitis ) Virus shed in feces

11. CLINICAL OUTCOMES There 3 possible outcomes Subclinical infection (90 - 95%) – accounts for majority cases, confer immunity and remain asymptomatic. Abortive infection (4 - 8%) -minor influenza-like illness occurs, recovery occurs within a few days D iagnosis can only be made by the laboratory. The minor illness may be accompanied by aseptic meningitis Major illness (1 - 2%) - may present 2 - 3 days following the minor illness or without any preceding minor illness. Signs of aseptic meningitis occur. Involvement of the anterior horn cells lead to flaccid paralysis. Involvement of the medulla may lead to respiratory paralysis and death.

12. CONT……… Abortive poliomyelitis:   the minor illness of poliomyelitis. Acute anterior poliomyelitis:   the major illness of poliomyelitis. Ascending poliomyelitis:   poliomyelitis with a cephalad progression. Bulbar poliomyelitis:   a severe form affecting the medulla oblongata, which may result in dysfunction of the swallowing mechanism, respiratory paralysis, and circulatory distress. Cerebral poliomyelitis:   poliomyelitis that extends into the brain. Spinal paralytic poliomyelitis:   the classic form of acute anterior poliomyelitis, with the appearance of flaccid paralysis of one or more limbs.

13. Contn Diagnosis . The available laboratory diagnostic tools include PCR I solation of the virus from cerebrospinal fluid, pharyngeal smear, or lavage, with the best chances of success from stool. Sero -diagnosis plays only a minor role . PREVENTION POLIO Administering oral and intramascular polio vaccine to children OPV- Against Type 1 & 2: Given at birth, at 1 and half month, at 3 month, 4 and half month and lastly 6month. IPV- Against Type 3: Given at 9months Routine mass immunization with OPV is done to all children 5yrs and below as strategies to eradicate the virus and incase of endemic out breaks

14. COXACKIEVIRUSES Named for the Coxsackie town, NY. Cause a variety of diseases; Group A : herpangina , acute hemorrhagic conjunctivitis, hand-foot and mouth disease Group B : pleurodynia , myocarditis and pericarditis Both: common cold, febrile rashes, aseptic meningitis Group A viruses have a predilection for skin and mucous membranes Group B causes disease in various organs like the heart, pleura, pancreas and liver Both viruses affect the meninges and the motor neurons

15. COXSACKIE A VIRUSES PATHOGENESIS CLINICAL MANIFESTATION Coxsackie A viruses spread through the fecal-oral and respiratory droplet The virus replicates in the epithelial cells of the throat and intestines before causing systemic viremia . L eading to skin and mucosal involvement. Fever, painful oral ulcers, and a vesicular rash on the hands, feet, and buttocks. Herpangina: Characterized by small vesicles and ulcers on the soft palate and uvula, accompanied by fever and sore throat.

16. HAND-FOOT-MOUTH DISEASE It is characterized by low grade fever, general malaise, oral and pharyngeal ulcerations and a vesicular rash or papulae on the palms, soles and buttocks, that may later spread to the arms and legs. Vesicles heal without crusting, which clinically differentiates them from the erosions for varicella , herpes simplex viruses and poxviruses . Caused by coxsackievirus A16 but also with B1 (and enterovirus 71 ). .

17. Virus may be recovered not only from the stool, pharyngeal secretions and vesicular fluid. It is not to be confused with foot and-mouth disease of cattle, which is caused by an unrelated picornavirus that does not normally infect humans. Coxsackievirus A6 causes severe hand-foot-and-mouth disease, sometimes followed by nail shedding

18. COXSACKIE B VIRUSES PATHOGENESIS CLINICAL MANIFESTATION After initial replication in the pharynx and intestines, the virus can spread to various organs, including the heart and pancreas. Coxsackie B viruses cause direct viral cytolysis of myocardial cells, triggering an inflammatory response. The host immune response can further damage cardiac tissue, exacerbating myocarditis. Myocarditis: Chest pain, dyspnea, arrhythmias, and signs of heart failure. Severe cases may progress to dilated cardiomyopathy. . Pericarditis: Inflammation of the pericardium, presenting with chest pain, friction rub, and evidence of pericardial effusion. Pleurodynia (epidemic myalgia): characterized by sudden, Stabbing chest pain and muscle tenderness, often called "devil's grip."

19. MYOCARDITIS Myocarditis is an acute inflammation of the myocardium It can progress to pericarditis with accumulation intrapercardial fluid. Perimyocarditis is a combination of both. Symptoms can include shortness of breath, chest pain, decreased ability to exercise, and an irregular heartbeat. The duration of problems can vary from hours to months. Complications may include heart failure due to dilated cardiomyopathy or cardiac arrest Myocarditis can progress to inflammatory cardiomyopathy when there are associated ventricular remodeling and cardiac dysfunction due to chronic inflammation

20. CONTN……… Mechanism of Myocarditis It involves cardiotropic viruses (viruses with a high affinity for gaining entry to cardiac muscle cells, usually via binding to a transmembrane receptors). Coxsackie B, specifically B3 and B5, interact with coxsackievirus -adenovirus receptor (CAR) and decay-accelerating factor ( DAF) and enter into mycardial cells. Over first week : The cell damage by virus leads to release of interleukins IL-6 and IL-8 and damage associated molecule patterns (DAMP). These mediate the recruitment of inflammatory cells of the innate immune system . P ro-inflammatory blood cells infiltration heart tissues: lymphocytes, macrophages and, NK cells.

21. CONTN………… L ater stimulate release of Tumor Necrosis Factor-α which binds on TNF-receptor 1, inducing necrosis and apoptosis of myocytes Additionally, any stress such as pain or anxiety triggers the medullary cells for monocytopoiesis and myeloid progenitor cells causing infiltration of neutrophils or eosinophils . The spleen is activated to replenish the pro-inflammatory cells. These mobilize and release lytic enzymes to the damaged myocardium, and release of interferon-gamma, that leads to further recruitment.

22. Contn …………. Over the next 2–4 weeks , viral replication continues with subsequent activation of the acquired immune system by activating Helper T cells, signaling leads to cytotoxic T cell infiltration in myocardium and signaling B cells to form antibodies, including the auto-antibodies . Auto-antibodies destroy the cardiac myosin chains The exaggerated inflammatory response to the viral damage of myocardium leads to chronic inflammation Over the next few months to years , this process either resolves and concludes with viral clearance. Or it may progress to cause permanent heart damage such as dilated cardiomyopathy, ventricular dysfunction or other cardiomyopathies

23. DIAGNOSIS: Normal ECG wave

24. Perimyocarditis tachycardia : PR segment depression diffuse ST elevation Lymphocitic myocarditis H & E tissue biopsy, showing lymphocytes and myocyte coagulative necrosis (-hyper- eosinophilic cytoplasm with loss of striations) ; later forms fluid.

25. Echocardiogram showing cardiac tamponade

26. ECHOVIRUSES PATHOGENESIS CLINICAL MANIFESTATIONS Many echoviruses have been associated with aseptic meningitis . Rashes are most common in young children. Infantile diarrhea may be associated with some types, but causality has not been established. Echoviruses spread similarly through fecal-oral and respiratory routes. These viruses show a predilection for various tissues, including the meninges, skin, and gastrointestinal tract. The immune-mediated response to echovirus infection can contribute to inflammation in affected tissues.

27. ROLE OF RHINOVIRUSES IN CAUSING COMMON COLD Rhinoviruses primarily infect the epithelial cells lining the nasal passages, throat, and sinuses. Once the virus enters the body, it attaches to receptors on the surface of these cells (especially via intercellular adhesion molecule-1 ICAM-1 receptors) . Replicates, and causes damage or inflammation in the affected tissues. The body’s immune response to rhinovirus infection is responsible for most of the symptoms of the common cold, such as a runny nose, sore throat, coughing, sneezing, and congestion. This is due to the release of pro-inflammatory cytokines and other immune mediators that help fight the virus but also cause swelling, mucus production, and irritation in the respiratory tract.

28. CONTN…….. Rhinoviruses come in different serotypes or strains, which makes it difficult for the immune system to develop long-lasting immunity . This is why people can get repeated colds throughout their lifetime, as exposure to one strain doesn't protect against others.

29. factors influencing high prevalence and transmission of rhinoviruses Rhinoviruses spread easily through respiratory droplets when an infected person sneezes, coughs, or talks. These droplets can be inhaled by others or land on surfaces that others touch, leading to infection via contact with the eyes, nose, or mouth. The fingers of a person with a cold are usually contaminated and transmission to a susceptible persons then occurs by hand to hand, hand to object contamination Rhinoviruses have a short incubation period (typically 1-3 days), meaning that symptoms can develop quickly after exposure. This rapid onset of symptoms allows the virus to spread before individuals realize they are infected. Infection rates are highest among infants and children and decrease with increasing age. ( Esp the preschool-aged and school-aged children). The family unit is a major site of spread of rhinoviruses. Rhinoviruses can survive for hours on contaminated environmental surfaces allowing indirect transmission. (I.E., By touch e.G doorknobs and phones).

30. REFERENCES Review of medical immunology,15 th edition by Warren Levison et.al Jawetz,Melnick and Adelberg’s Medical immunology 28 th Edition by Stefan Riedel et.a l