Hepatitis B and Picinaviridea viruses pptx.pptx

Hepatitis B and Picinaviridea virus

1. KAWULUKA ALAMANZANI VU-BPC-2209-0430-DAY 14 KAWALYA STEVEN VU-BPC-2307-0639-DAY KATUSIME JULIAN VU-BPC-2307-0167-DAY KATAZA HEZRON VU-BPC-2209-1312-DAY GROUP 14

2. Question 26 Hepadnaviridae : Hepatitis B virus What are the structural and genomic characteristics of Hepatitis B virus, and how do these features contribute to its ability to establish chronic infections in humans? Explain the mechanisms of Hepatitis B virus transmission. How do different transmission routes contribute to the global epidemiology of HBV infection? Discuss the pathogenesis of Hepatitis B virus infection, highlighting the differences between acute and chronic infections, and the virus’s role in the development of liver cirrhosis and hepatocellular carcinoma. What are the current strategies for the prevention and treatment of Hepatitis B, including the role of the Hepatitis B vaccine and antiviral therapies? How effective are these approaches in managing the global burden of HBV infection?

3. A double stranded DNA vir us, a species of the genus Orthohepadnavirus , and a member of the Hepadna viridae family of viruses . HBV causes the disease hepatitis B . Hepatitis B virus

4. This unprecede nted recovery of ancient virus DNA indicates that H B V was c irculating in Europe at least 7000 years ago . The oldest virus ever found is an STI

5. Structure

6. • HBV a member of the hepadnavirus gr oup • double - stra nded DNA viruses which replicate by reverse transcript ion . • 42-nm in size • HBV express three main antigens : 1. HBsAg - surface antigen 2. HBcAg - core antigen 3. HBeAg - envelope antigen • These antigens are recognized by an tibody proteins that bind spe cifically to one of these surface proteins Structure

7. Cont

8. Nucleocapsid is 27 nm in diameter surrounded by a n outer envelope of the surf ace protein ( HBsAg ) embedded in membr anous lipid derived from the host cell also known as the Australia antigen . It indicates current hepatitis B infect ion . Positive HBsAg tests can be due to recent vaccination against HBV but this positivity is unl ikely to persis t beyond 14 days post - vaccination It is present in the sera of patients with viral hepatitis B ( with or without clinical symptoms ). Structure / HB sAg

9. • HBcAg ( core antigen ) is a hepatitis B viral prot ein. • It is an indicator of active viral replication • This means the person infected with Hepatitis B can likely transmit the virus on to another person. • HBcAg is not secreted . HBcAg is considered " particulate " and it does not circulate in the blood . • I t is readily detected in hepatocytes after biops y • The presence of both HBcAg and HBeAg proteins together act as a marker of viral replication , and antibodies t o these antigens area marker of declining replication. Structure / HBcA g

10. • It is an indicator of active viral replication ; th is means the person infected with Hepatitis B can l ikely transmit the virus on to another person. • can be found be tween the icosahedral nucleocapsid core and the lipid envelope • HBeAg is considered " nonparticulate " or " secretory ". • HBeAg is secreted and accumulates in serum as an immunologic ally distinct soluble antigen. • The presence of HBeAg in the serum of patients can serve as a marker of active replic ation in chronic hepatitis. Structure / HB eAg

11. Life cycle of the HBV.

12. Multiplication /

13. • O ne of a few known non - retroviral viruses which use reverse transcription • The virus gains entry into the cell by binding to recepto rs on the surface of the ce ll and entering it by endocytosis mediated by either C lathrin or C aveolin-1 . • HBV initially binds to heparin sulfate proteo glycan • Following endocytosis , the virus membrane fuses with th e host cell ' s membrane , releasing th e nucleocapsid into the cytoplasm Multiplication

14. • T he viral genomic DNA has to be tr ansferred to the cell nucleus . • The core proteins dissociate from the partially do uble stranded viral DNA , which is then mad e fully double stranded (by host DNA polymerases ) and transformed into covalently close d circular DNA ( cccDNA ) that serves as a template for transcription of four vira l mRNAs . • The largest mRNA , ( which is longer than the viral genome ), is used to make the new copi es of the genome and to make the capsid core protein and the viral RNA-dependant-DNA-polymerase. Multiplication

15. STAGES OF THE DISEASES FIRST STAGE The duration of this stage for healthy adults is approximately 2-4 weeks and coincide with the incubation period . on average but can vary from 30 to 180 days. For newborns, the duration of this period often is decades. Active viral replication is known to continue despite little or no elevation in the aminotransferase levels and no symptoms of illness. 15

16. SECOND STAGE In the second stage, an inflammatory reaction with a cytopathic effect occurs. HBeAg can be identified in the sera and a decline of the levels of HBV DNA is seen. The duration of this stage for patients with acute infection is approximately 3-4 weeks (symptomatic period). For patients with chronic infection, 10 years or more may elapse before cirrhosis develops. 16

17. THIRD STAGE In the third stage, the host can target the infected hepatocytes and the HBV Viral replication no longer occurs. HBeAb can be detected. The HBV DNA levels are lower or undetectable, and aminotransferase levels are within the reference range. In this stage, an integration of the viral genome into the host's hepatocyte genome takes place. HBsAg still is present. 17

18. FOURTH STAGE In the fourth stage, the virus cannot be detected and antibodies to various viral antigens have been produced . Different factors have been postulated to influence the evolution of these stages, including age, sex, immunosuppression , and co-infection with other viruses. 18

19. PATHOLOGY Three antigen-antibody systems 1) HBsAg -- anti-HBs system: HBsAg appears 1-2 weeks (late up to 11-12 weeks) after exposure, persists for 1-6 weeks( even 5 months) in acute hepatitis B. In chronic patients or carrier, HBsAg persist many years HBsAg is the marker of infectivity 19

20. HBsAg can be found in blood and secretions: saliva, urine, semen, tears, sweat and breast milk Anti-HBs appear after HBsAg disappear several weeks (or months) anti-HBs is protective antibody, can persist for many years 20

21. 2) HBcAg —anti- HBc system HBcAg can be found in the nuclei of liver cells, no free HBcAg in serum HBcAg is the marker of replication of HBV The stage called window phase Anti- HBc IgM is a marker of acute infection and acute attack of chronic infection of HBV. Anti- HBc IgG is the marker of past infection, high titer means low level replication of HBV. 21

22. 3) HBeAg —anti- HBe system HBeAg is a soluable antigen HBeAg is a reliable indicator of active replication of HBV Anti- HBe is a marker of reduced infectivity. If exist long may be a marker of integration of HBV into liver cell 22

23. • Hepatitis B virus primarily inte rferes with the functions of the liver by replicating in hepatocytes . • virions bind to the hos t cell via the viral surface antigen and are subsequently internalized by endocy tosis. HBV specific receptors are expressed pri marily on hepatocytes • During HBV infection , the host imm une response causes both hepatocellular damage and viral clearance . • Most liver injury is caused by c ytotoxic T lymphocytes Pathogene sis

24. HBV causes hepatocel lular carcinoma • An HBV protein traps protons and Cl −, and induces the expression of collagen in the liver, which forms potent hydrogen bonds wit h trapped prot ons . • The presenc e of collagen in the liver marks the progression to fibrosis . • Virus can cause inactivation tumor suppressor genes, or activation of oncogenic genes like C yclin A • Translocation and chromosomal arrangements also h ave been seen Pathogenesis of Canc er

25. Acute Infectio n • Symptoms of acute HBV infection are non - specific and include fatigue, poor appeti te, nausea, vomiting, abdominal pain, low-grade fever, jaundice , and dark urine . • itchy skin is a possib le symptom of all hepatitis virus types • liver tenderness , hepatomegaly , and splenome galy • it can lead to fulminan t hepatic failure and may die or require emergent liver transplantation . • The infection may be entirely as ymptomatic and may go unrecognized Symptoms

26. 26

27. Chronic Infectio n • HBV infection is considered chronic when it persists longer than six months • asymptomatic or may be associated with a chronic inflammation of t he liver – Chronic hepatitis • Coinfection with human immunodeficiency virus ( HIV ) or hepatitis C virus can occur • It can lead to liver cirrhosis • increases the incidence of hepatocellula r carcinoma (HCC; liver cancer ) • Acute necrotizing vasculitis,glomerulonephritis, jaundice, fever, skin rash, and polyarteritis . • Nephropathy, anemia Symptoms

28. 28

29. Cont

30. High-risk groups for HBV infection People from endemic regions Babies of mothers with chronic HBV Intravenous drug abusers People with multiple sex partners Hemo dialysis patients Health care personnel who have contact with blood Residents and staff members of institutions for the mentally retarded 30

31. MODES OF TRANSMISSION Sexual - sex workers and homosexuals are particular at risk. Parenteral - IVDA, Health Workers are at increased risk. Perinatal - Mothers who are HBeAg positive are much more likely to transmit to their offspring than those who are not. Perinatal transmission is the main means of transmission in high prevalence populations. 31

32. 32 Perinatal transmission Horizontal transmission Mother Infant Host Perinatal 90% of infected infants become chronically infected 6% of people infected over the age of 5 become chronically infected Recipient Child-to-child Contaminated needles Sexual contacts Healthcare worker Blood transfusion

33. Serum transaminases • Once an individual has been diagnosed with ch ronic HBV infection, follow-up testing must be performed for alanine aminotransferase ( ALT ), a marker of liver cell inflammation HBV - DNA • The presence of HBV - DNA in serum or plasma denotes active HBV infection and, depending on the viral load, correlates with the infectivity of the patient . Diagnosis

34. • evaluation of the patient's blood for • HBsAg • hepatitis B surfa ce antibody ( HBsAb ) • hepatitis B core antibody ( HBcAb ) • presence of HBsAg indicates that the perso n is infectious • presence of HBsAb indicates recovery and immunity from HBV infection or successful immunization against HBV . • HBcAb appears at the onset of acute HBV infection, but may also indicate chronic HBV infection. Diagnosis

35. Prevention Strategies Hepatitis B Vaccination Schedule : Three doses at 0, 1, and 6 months. Immune Response : Induces protective Anti-HBs antibodies. Antibody Titer Measurement : Responders : Titer ≥ 100 IU/L, adequate immunity. Hyporesponders / Nonresponders : May need additional doses. Booster Doses : Not routinely required due to immunological memory. Passive Immunization Human Anti-HBs Immunoglobulin (HBIG) : Usage : After high-risk exposure (e.g., needlestick injuries). Effectiveness : Provides short-term protection if administered promptly . Tenofovir : given in the 2nd or 3rd trimest er , to reduce the risk of mother to child transmission PREVENTION STRATEGIES

36. Goals of Treatment Reduce Viral Replication : Lower viral load. Slow Disease Progression : Prevent cirrhosis and liver cancer. Common Antiviral Agents Nucleoside/Nucleotide Analogs : Examples : Tenofovir, entecavir. Function : Inhibit HBV DNA polymerase. Pegylated Interferon-alpha (IFN- α) : Function : Boosts immune response against HBV. Treatment Considerations Long-Term Therapy : Often required to prevent viral rebound. Not Curative : Controls but does not eradicate the virus. Drug Resistance : Newer drugs have higher resistance barriers . Antiviral Therapies

37. Effectiveness and Global Impact Vaccination Success Reduced Incidence : Significant drop in HBV rates where vaccination is widespread. Lowered HCC Rates : Decrease in liver cancer associated with HBV. Challenges Vaccination Coverage Gaps : Especially in low-income countries. Mother-to-Child Transmission : Continues to be a significant issue. Access to Treatment : Limited availability of antivirals in some regions. Ongoing Efforts Expand Vaccination Programs : Especially in high-prevalence areas. Improve Healthcare Practices : Safe medical procedures and sterilization. Increase Treatment Access : Make antiviral therapies more widely available.

38. PICORNAVIRIDAE

39. 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?

40. 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

41. 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 vira l protein (VPg ). Genome 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.

42. ENTERO VIRUSES Genome: Positive-sense single –stranded RNA Viruses Transmission : Named based on transmission route through intestines Classified into four groups Polio viruses Coxsackie A viruses – CA Coxsackie B viruses – CB Enchoviruses

43. ENTEROVIRUSES, RHINOVIRUSES AND HEPATITIS A REPLICATION Viral entry ; Virus binds to enterocytes via following receptors 1. FcRn - ( Neonatal fragment crystallisable receptor ) It is hijacked by virions and then uncoats the virus . Located on GIT mucosal cells, lungs and brain. 2. DAF/CD - ( Decay Accelerating factors/Complement d ecay accelerating factor) Receptor for attachment of RNA and cause its transcytosis into the cytoplasm. CD155: for Poliovirus CD55: for CV-B ICAM-( Intercellular adhension molecule): for CV-A21 AND CV-A24 SCARB2 (Scavenger receptor B2) and PSGL-1 (P- selectin glycoprotein ligand-1 for CV-A

44. CONTN…………….. Enterovirus replication 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 template for translation of viral proteins VPg . VPg translation is driven by Internal Ribosome E ntry S egment in 5 1 - NTR 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

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

46. PATHOGENESIS OF ENTERO VIRUSES V iruses are easily ingested in GI tract to infect host cells in GIT 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) Can systemic spread of virus through lymph and blood.

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

48. 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 or CD155 ( Complement decay-accelerating factor) on human 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.

49. 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

50. 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.

51. 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.

52. 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 1,2 & 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

53. Hepatitis A Virus (HAV ) Transmission Routes Fecal-Oral Transmission Contamination: food and water Entry: Binds on Hepatitis A virus cellular receptor -1/T-cell immunoglobulin receptor 1 Indirect Transmission: Contaminated surfaces and objects Travel to Endemic Areas: Higher prevalence in regions with lower sanitation standards Diagnosis Based on IgM detection due to the early presence of these antibodies in patient serum. I n fact so early that, a lack of hepatitis A antibodies at the onset of clinical manifestations excludes hepatitis A .

54. Cont Clinical Outcomes Incubation Period: 15 to 50 days (average ~28 days) Symptoms: Fever, fatigue, nausea, abdominal pain (especially in the upper right quadrant), jaundice Disease Course: Usually self-limiting and benign Does not cause chronic hepatitis Immunity: Exposure to infection leads to lifelong immunity

55. Cont Prevention Strategies Vaccination: Inactivated HAV vaccine (two doses, six months apart) Recommended for travelers and high-risk groups Sanitation and Hygiene: Handwashing, safe water and food practices Public health education Passive Immunization: Immunoglobulin administration for short-term protection

56. Differences of HBV from Hepatitis B and C Category Hepatitis A Virus (HAV) Hepatitis B Virus (HBV) Hepatitis C Virus (HCV) Transmission Routes Fecal-Oral Route: Through contaminated food or water. Bloodborne: Parenteral, sexual contact, perinatal transmission. Blood borne : Primarily via sharing needles. No Blood borne Transmission: Rarely transmitted via blood. Modes: Sharing needles, needle-stick injuries, and personal items. Less Common Transmission: Sexual contact, perinatal transmission. Clinical Outcomes Acute Infection Only: Does not lead to chronic disease. Acute and Chronic Infection: 5-10% of adults develop chronic infection. High Rate of Chronic Infection: 75-85% develop chronic infection. Self-Limiting: Most recover completely with no liver damage. Long-Term Complications: Chronic hepatitis, cirrhosis, liver cancer. Long-Term Complications: Chronic hepatitis, cirrhosis, liver cancer. Immunity: Lifelong immunity after infection. Carrier State: Asymptomatic carriers possible. Often Asymptomatic Initially: Many are unaware until significant liver damage.

57. Cont Category Hepatitis A Virus (HAV) Hepatitis B Virus (HBV) Hepatitis C Virus (HCV) Prevention Strategies Vaccination: Highly effective, recommended for high-risk groups. Vaccination: Safe and effective, part of childhood immunization programs. No Vaccine Available: High genetic variability prevents vaccine development. Sanitation and Hygiene: Improved water supply, hygiene education. Preventing Transmission: Safe sex, blood screening, antiviral prophylaxis. Preventing Transmission: Safe injections, screening blood, harm reduction. No Chronic Infection: No carrier state. Treatment: Antiviral medications manage but may not cure chronic infection. Treatment: Direct-acting antivirals (DAAs) can cure most cases. Key Differences Fecal-oral transmission, no chronic infection, vaccination available. Bloodborne, risk of chronicity, vaccination available. Bloodborne, high chronicity, no vaccine, curable with DAAs.

58. COXSACKIE VIRUS

59. COXSACKIE VIRUS Member of the Picornaviridae family of viruses in the genus termed Enterovirus . Coxsackieviruses are subtype members of single strand of ribonucleic acid (RNA) for its genetic material. 24- 30 nm spherical naked, icosahedral + ssRNA multiply in cytoplasm At least 23 serotypes of group A And 6 serotypes of group B

60. COXACKIEVIRUSES Named for the Coxsackie town, NY. Cause a variety of diseases; Group A : H erpangina , 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

61. TRANSMISSION C oxsackieviruses are contagious person to person. These viruses are transmitted mainly by the faecal-oral route and by respiratory aerosols. Droplets containing viruses that land on objects like toys or utensils may occasionally transmit the viruses indirectly to uninfected individuals.

62. INCUBATION PERIOD The incubation period for coxsackievirus infections is relatively short It lasts about 1 to 2 days with a range of about one to 5 days.

63. 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. Coxsackie A16 majorly causes Hand, foot and mouth disease Fever, painful oral ulcers, and a vesicular rash on the hands, feet, and buttocks. Conjuctivitis Herpangina : Characterized by small vesicles and ulcers on the soft palate and uvula, accompanied by fever and sore throat.

64. 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 C oxsackievirus A16 and CV- B1 ( also E nterovirus 71 ).

65. 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 A16 causes severe hand-foot-and-mouth disease, sometimes followed by nail shedding

66. 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 . Perimyocarditis is a combination of both. Pleurodynia (epidemic myalgia): characterized by sudden, Stabbing chest pain and muscle tenderness, often called "devil's grip ."

67. 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) or CD55 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.

68. 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 to produce neutrophils, eosinophils and monocytes which infiltrate into the myocardium. The spleen is also activated to replenish more pro-inflammatory cells. These mobilize and release lytic enzymes to further more damage the myocardium, and release of interferon-gamma, that leads to further recruitment.

69. 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 and myocardio - fibrosis CBV binds on Toll-Like receptors TLR ; This exaggerates inflammatory response to the viral damage of myocardium, leading 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 heart failure due to dilated cardiomyopathy and ventricular dysfunction or cardiac arrest .

70. DIAGNOSIS ECG: Normal ECG wave

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

72. Echocardiogram showing cardiac tamponade

73. DIAGNOSIS Patients are usually diagnosed by their clinical appearance . Clinically, blisters that are painful usually on the hands, feet, and mouth in a child with fever are considered diagnostic of coxsackievirus infection . Diagnostic laboratory that uses RT-PCR, and often take about two weeks to get a result.

74. TREATMENT N o specific treatment for this typically self-limited disease (the symptoms resolve without specific antiviral treatment in about two to 10 days). S ymptomatic acetaminophen that reduces fever and discomfort is currently recommended. Mouthwashes and sprays may lessen the oral discomfort. Fluids prevent dehydration, acidic juices may irritate the mouth ulcers. Home remedies like cold milk may sooth the oral discomfort . T opical diphenhydramine containing gel or liquids to treat the hand and foot discomfort.

75. ECHOVIRUSES PATHOGENESIS CLINICAL MANIFESTATIONS Many echoviruses have been associated with aseptic meningitis . Rashes are most common in young children. GIT - 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.

76. Rhinovirus Common Cold Common Cold Rhinovirus is best known as the common cold. It is a member of the picornaviridae family along with more virulent viruses such as polio and hepatitis A

77. Rhinoviruses Rhinoviruses are the most commonly isolated viruses from persons with mild Upper R espiratory Tract illness . In contrast to enteroviruses they do not replicate in the intestinal tract, they have an extreme species specificity and more fastidious growth requirements Classified into three species RV-A, B and C, with over 160 types Receptors for Entry: Intercellular adhension molecule-1 receptor ( ICAM-1 ): RV-A Low Density Lipoprotein receptor (LDLR ) : 12RV-A types Cadherin- related family member-3 receptor ( CDHR3 ): RV-C

78. 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 cells surface (esp. ICAM-1 receptors) and cross into the cytoplasm by endocytosis 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.

79. CONTN…….. Rhinoviruses come in different immunity. serotypes or strains, which makes it difficult for the immune system to develop long-lasting This is why people can get repeated colds throughout their lifetime, as exposure to one strain doesn't protect against others . Young children are more likely to have the frequent, close, personal contact necessary to transmit RV They commonly pass the infection to family members after acquiring the virus in nurseries, daycare facilities, and schools . Children may also be more contagious by virtue of having higher virus concentrations in secretions and longer duration of viral shedding .

80. Pathogenesis of rhinovirus infections

81. Organs Affected Colds are usually harmless and clear up without any serious consequences. But  bacteria can sometimes spread through the airways after a viral infection, and they may cause more severe problems in different places, such as in the sinuses. An infection in your voice box (larynx) can cause you to lose your voice . In babies, infants and young children, colds sometimes spread to the ear and cause a middle ear infection ( ottitis media).   Streptoccocal bacterial infections  in the throat can cause a sore throat or tonsillitis . Infections of the upper airways very rarely cause serious complications like  pneumonia

82. Signs and Symptoms Most people get colds in the winter and spring, but it is possible to get a cold at any time of the year. Symptoms usually include sore throat , runny nose , coughing , sneezing , watery eyes , headaches and body aches . Most people recover within about 7-10 days. However , people with weakened immune systems, asthma, or respiratory conditions such as chronic obstructive pulmonary disease (COPD). may develop serious illness, such as pneumonia. Presenting with high  fever, severe or worsening symptoms, chest pain, shortness of breath or trouble breathing .

83. Natural Remedy Turn up the heat Stay hydrated Soothe your skin Gargle salt water Herbal supplements Prevent the spread Medical Management There's no cure for the common cold. Antibiotics are of no use against cold viruses . OTC cold preparations won't cure a common cold or make it go away any sooner, and but most have side effects. Pain relievers Decongestant nasal sprays Cough syrups Supplements- zinc,  vitamin C , and echinacea .

84. Factors Influencing Prevalence and Transmission Multiple Serotypes: 117 known serotypes; immunity to one doesn't protect against others Brief Immunity: Short-lived immune response allows reinfection No Latency: incubation period (typically 1-3 days), Infections are always due to new exposures Transmission Modes: Direct contact (contaminated hands) Droplet infection (coughing, sneezing ) Environmental Factors: Winter prevalence due to indoor crowding Virus thrives in cooler, less humid conditions Human Behavior: Hand-to-face contact, inadequate hand hygiene Common among preschool and school children

85. Conclusion Picornaviridae structural and genomic features enable adaptation to various environments. Enteroviruses can survive acidic GI tract conditions, leading to systemic infections. Rhinoviruses are adapted to the upper respiratory tract, causing common colds. HAV is transmitted via the fecal-oral route, causing self-limiting hepatitis A. Understanding these viruses aids in prevention, diagnosis, and treatment strategies.

86. 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.al END