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Group microbiologypresentation final.pptx
- 1. GROUP 5 PRESENTATION NSAMBA GEORGEWILLIAM VU-BPC-2301-0132-DAY NSUBUGA WILBERFORCE VU-BPC-2301-0024-DAY NTEGE ABUDALLAH VU-BPC-2307-1132-DAY NUWAHA RODGERS VU-BPC-2307-0188-DAY OBIN DERRICK VU-BPC 2307-0315-DAY
- 2. Question • Human Cytomegalovirus(HCMV) • • Describe the structure of HCMV and how it differs from other herpesviruses. • • How is HCMV transmitted, and what makes congenital CMV a significant concern? • • What are the clinical manifestations of HCMV in immunocompromised individuals and • newborns? • • Discuss the antiviral treatments available for HCMV and how they target the virus’s replication
- 3. • Human Herpesvirus6 & 7 (HHV-6 & HHV-7) • • What are the structural similarities and differences between HHV-6 and HHV-7? • • How are HHV-6 and HHV-7 transmitted, and what is the clinical presentation of roseola • infantum? • Discuss the complications of HHV-6 reactivation, particularly in immunocompromised • patients. • • What diagnostic methods and treatments are available for HHV-6 and HHV-7 infections?
- 4. HUMAN CYTOMEGALO VIRUS •Cytomegalovirus or human herpesvirus 5 (HSV-5) is the causative agent of mononucleosis syndrome in symptomatic infection in immunocompetent hosts • It causes pneumonia and more serious diseases in immunocompromised patients than in other individuals • The name is originated from the word cytomegalo (large cell virus) and is derived from the swollen cells containing large multinuclear inclusions that characterize these infections.
- 5.
- 6. • Genome • HCMVhas a large double -stranded DNA genome (~230kb) • The genome is divided into Unique long and Unique short regions flanked by inverted repeats. • Capsid • The capsid is icosahedral, approximately 130 nm in diameter, composed of 162 capsomers. • Tegument • Surrounding the capsid is the tegument, a protein layer that contains viral proteins and mRNA. • Envelope • The outermost layer is the lipid envelope, embedded with glycoproteins essential for viral entry into host cells.
- 7. • Differences fromother herpesviruses: • Larger genome compared to HSV-1 (Herpes Simplex Virus) and VZV (Varicella-Zoster Virus). • Higher genetic diversity and variability.
- 8. • Classification • HCMVis a double-stranded DNA virus and the largest human herpesvirus in terms of size. • HCMV, also known as human herpesvirus 5 (HHV-5), is a member of the Herpesviridae family
- 9. • Domain: Eukarya •Kingdom: Animalia • Phylum: Chordata • Class: Mammalia • Order: Primates • Family: Herpesviridae • Subfamily: Beta herpes virinae • Genus: Cytomegalovirus
- 10. • Cytomegalovirus sharessimilar common features in the structure, genome, and potency to cause latent and persistent infections like those of other herpesviruses •Morphology • CMV is the largest herpesvirus measuring 150–200 nm in size • It has the largest genome of all the herpesviruses, ranging from 230 to 240 kbp. It is a double-stranded linear DNA virus with 162 hexagonal protein capsomeres surrounded by a lipid membrane.
- 11. Pathogenesis and Immunity •CMV is a lytic virus, which produces the CPE in vitro and in vivo. The pathogenesis of CMV infection is similar to that of other herpesviruses in many ways. • Pathogenesis of CMV infection • The virus infects the epithelial cells of the salivary glands, causing a persistent infection and shedding of viruses in the salivary secretion • Activation and multiplication of the virus in the kidney and secretory glands facilitate secretion of CMV in urine and other body secretions including serum and milk • CMV infection is acquired by coming in contact with blood, tissue, and most body secretions containing viruses. On entering the human host, CMV primarily affects epithelial cells and causes infection of those cells
- 12. • Subsequently, CMVinfection progresses to establish persistent and latent infection in T cells, macrophages, and other cells and in different organs, such as the kidney and heart. • . In the infected cells, CMV infection produces characteristic enlarged cells with viral inclusion bodies • This histopathological change, most commonly referred to as owl’s eye, is considered diagnostic of the CMV infections. These histological findings, however, may be minimal or absent in infected organs.
- 13. • Host immunity •Immunity to CMV involves both humoral immunity and Cell Mediated Immunity (CMI). • CMI is more important and essential (a) for resolution of infection and (b) also for controlling progression of CMV infection. • The production of cytotoxic T cells against CMV is very crucial in CMI response to control the infection. CMV-specific CD4 and CD8 lymphocytes play an important role in protection after primary infection or reactivation of latent disease
- 14. • Studies haveshown that patients who do not develop CMV-specific CD4 or CD8 cells are at higher risk for developing CMV pneumonitiss • . Suppression of CMI, which is caused by therapy with corticosteroid or infection with HIV, induces reactivation of the latent viral infection • The humoral immunity is characterized by development of CMV IgM antibodies during 4–7 weeks of infection.
- 15. • These neutralizingantibodies are directed mostly against an envelope glycoprotein gB. More than 50% of neutralizing antibodies in convalescent serum are found to be produced against glycoprotein Gb • Antibodies are also produced against other viral proteins, such as pp153, pp28, and pp65. • . The antibodies have some role in control of severe disease, but do not prevent trans placental infection, which can occur even in pregnant mothers who are CMV seropositive
- 16. Clinical Syndromes CMVcauses • (a) congenital CMV infection, (b) acquired CMV infection, (c) CMV infection in immunocompromised patients, and (d) CMV infection in immunocompetent adult hosts. • ◗ Congenital CMV infection • CMV is the most common viral cause of congenital infection. The infection is acquired by fetus by transmission of virus through placenta from mother’s blood.
- 17. • The infectioncan also be an ascending infection from the cervix of the mother during recurrence of infection. The congenital infection may be classified as asymptomatic or symptomatic. • Asymptomatic congenital CMV infection occurs in infants born to women who have preexisting immunity to CMV. These infants appear normal at birth but are at risk of developing growth retardation and other neurodevelopmental abnormalities during later stage of life.
- 18. • Cytomegalic inclusiondisease is the manifestation of the symptomatic congenital CMV infection, which usually occurs in women who acquire primary CMV infection during pregnancy. The disease is characterized by microcephaly, intracerebral calcification, hepatosplenomegaly, and rash. • Mental retardation and unilateral or bilateral hearing loss are the most common consequences of cytomegalic inclusion disease in adults. Approximately, 10% of affected infants show clinical evidence of disease at birth.
- 19. • ◗ AcquiredCMV infection Acquired CMV infection occurs postnatally as follows: Perinatal CMV infection: This condition usually occurs following exposure to infected genital secretions in the birth canal or to milk during breast feeding. • Most perinatal infections are asymptomatic. Some infants may manifest lymph adenopathy, hepatitis, and pneumonitis • However, these patients do not show any neurological or neurodevelopmental complications. CMV mononucleosis: CMV mononucleosis is a disease of young adults acquired by person-to-person transmission.
- 20. • This conditionis transmitted by blood transfusion or organ trans plantation. Fever and severe malaise are typical symptoms. Clinically, it is difficult to distinguish CMV mononucleosis from EBV-induced mononucleosis • Transfusion-acquired CMV infection: This condition occurs following transfusion of infected blood after an incubation period of 20–60 days. • This condition is mostly asymptomatic. In symptomatic cases, clinical manifestations of transfusion-acquired CMV are similar to CMV mononucleosis.
- 21. • ◗ CMVinfection in immunocompromised host • CMV is the most important opportunistic agent in immunocompromised hosts, in whom it causes a variety of clinical syndromes. These include life-threatening intestinal pneumonitis, gastrointestinal diseases, retinitis, hepatitis, encephalitis, and varieties of other CMV syndromes. Patients receiving organ transplants are severely affected by the disease • CMV infection in immunocompetent adult hosts • CMV produces mononucleosis syndrome, a condition similar to EBV-induced mononucleosis in immunocompetent adult hosts. CMV is a sexually transmitted disease
- 22. • The infectionis transmitted by contaminated genital secretions. Epidemiology CMV infection is worldwide • Geographical distribution • Many serological surveys have shown CMV to be present in 42–100% of the people depending on socioeconomic condition
- 23. • In developingcountries, infection of children is most common with a seroprevalence for CMV to be 100% very early in child hood. In developed countries, infection of the young adults is more common; more than 50% of young adults are seropositive in many developed countries. • ◗ Reservoir, source, and transmission of infection Humans are the natural hosts. . An infected human is the only reservoir of CMV infection. No animal reservoirs are present for this virus. Cytomegaloviruses are found in the urine, blood, saliva, tears, throat swab, stool, semen, milk, amniotic fluid, cervical and vaginal secretions, and tissue obtained for transplantation • Saliva, tears, urine, and breast milk are the common sources of infection for baby or child
- 24. • . Cervicalsecretions are the source of transmission of infection to neonates. Blood, organ graft, and semen are the other sources of infection in adult popula tion. Transmission of CMV occurs in a variety of ways: • ■ Early in life, infection is transmitted to infants through the placenta, through infected birth canal, and also through breast milk • Infection to young children is most commonly transmitted by saliva. • In adults, infection is transmitted sexually through semen and cervical secretions
- 25. • Infection isalso transmitted through the blood transfusion and organ transplantation. CMV causes latent infection; hence reactivation may result in disease in patients who are immunocompromised. • These patients include those with HIV and those receiving organ and bone marrow transplantation. Immunodeficiency caused by antineoplastic compounds and ionizing radiation may also cause reactivation of CMV infection. • Immune compromised Individuals • HCMV infection in immunocompromised individuals, such as those with HIV/AIDS, organ transplant recipients, or those undergoing chemotherapy, can lead to a variety of serious complications. Some of the most common clinical manifestations include:
- 26. • Retinitis: Inflammationof the retina, which can lead to vision loss or blindness • Pneumonitis: Inflammation of the lungs, causing symptoms like cough, shortness of breath, and fever. • Gastroenteritis: Inflammation of the gastrointestinal tract, resulting in diarrhea, abdominal pain, and nausea • Encephalitis: Inflammation of the brain, leading to symptoms like headache, fever, confusion, and seizures.
- 27. • Bone marrowsuppression: HCMV can interfere with bone marrow function, leading to anaemia, neutropenia, and thrombocytopenia • Newborns • Asymptomatic infection presents since many infected newborns experience no symptoms. • Hearing loss: The most common long-term complication of cCMV.
- 28. • Vision problems:Retinitis, a condition that can cause vision loss or blindness • Intellectual disability: Delayed development and cognitive impairments. • Seizures: Seizures can occur in some cases. • Liver and spleen enlargement: Hepatosplenomegaly. • Jaundice: Yellowing of the skin and eyes.
- 29. Laboratory Diagnosis • SpecimensDifferent body secretions, such as saliva, urine, throat washing, blood, CSF, cervical secretions, and bronchoalveolar lavage fluid, and tissue bits are the specimens that can be used for the culture • Treatment • Ganciclovir is the drug of choice for treatment of CMV. It is a nucleoside analog that inhibits DNA synthesis and also has activity against HSV, and human herpesviruses 7 and 8.
- 30. • Mechanism ofaction • It works by interfering with the viral replication cycle. • Ganciclovir is taken up by cells through a process called active transport. • Once inside the cell, ganciclovir is phosphorylated by cellular enzymes. This phosphorylation process is essential for activating the drug. • The phosphorylated form of ganciclovir is incorporated into the viral DNA during viral replication.
- 31. • Once incorporated,ganciclovir acts as a chain terminator, preventing the virus from further replicating its DNA. This is because ganciclovir lacks the necessary hydroxyl group for the addition of more nucleotides to the DNA chain. • By inhibiting viral DNA replication, ganciclovir effectively prevents the production of new viral particles, thereby limiting the spread of the infection. • Neutropenia and thrombocytopenia are the major adverse effects associated with ganciclovir therapy. • Foscarnet is another drug, which has been used to treat the infection that is resistant to ganciclovir.
- 32. • Prevention andControl • Sexual transmission of CMV can be prevented by following safe sexual practices, such as using condoms. Transmission of virus is also reduced by regular screening of blood and organ donors for CMV seronegativity. • Prophylaxis with ganciclovir prevents reactivation of latent CMV infection in immunocompromised patients. No vaccine is available for CMV
- 33. • Human Herpesvirus6 • Human herpesvirus 6 (HSV-6) was first isolated from the peripheral blood of patient with AIDS in the year 1986. HSV-6 like EBV and CMV is lymphotrophic and ubiquitous. • . This virus is believed to persist chronically in salivary gland tissue in some of the adults. The virus is spread by the saliva, which is the main source of infection. Like other herpesviruses, HSV-6 causes a latent infection in T cells and monocytes.
- 34. • The replicationof the virus in CD4 T lymphocytes is controlled by CMI. The reactivation of the virus occurs in immunocompromised patients (patients with AIDS or other immunosuppression disorders). HSV-6 causes roseola infantum, a febrile infection that affects young children. • The virus may also cause mononucleosis syn drome and lymphadenopathy
- 35. • Human herpesvirus7 (HSV-7) • Human herpesvirus 7 (HSV-7) was first isolated from peripheral CD4 cells of healthy persons in 1990. HSV-7 like HSV-6 has also been isolated from saliva of healthy adults and has been implicated as one of the causative agents of rubeola infantum and febrile seizures in children. • The virus has also been associated with acute hemiplegia of childhood, hepatitis, and respiratory tract infections. • Human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) share many structural similarities and differences.
- 36. • Similarities: • Bothviruses are enveloped, meaning they have a lipid bilayer membrane surrounding their capsid. • The capsid, the protein shell that encloses the viral genome, is icosahedral in shape for both HHV-6 and HHV-7. • Both viruses possess double-stranded DNA genomes
- 37. • Differences: • HHV-6generally has a slightly larger genome than HHV-7. • While both viruses share many genes, there are differences in the specific genes they encode, which can influence their biological properties. • HHV-6 tends to establish a more persistent, latent infection in host cells, while HHV- 7 may exhibit a more lytic (productive) infection cycle. • Transmission of HHV-6 and HHV-7
- 38. • Both HHV-6and HHV-7 are highly contagious and can be transmitted through: • Respiratory droplets by coughing, sneezing, or close contact with an infected person. • Saliva: Sharing food or utensils with an infected person. • Blood: Blood transfusions or organ transplantation
- 39. • Roseola infantum •This is a common childhood illness caused primarily by HHV-6, but can also be caused by HHV-7. It typically affects children between the ages of 6 months and 3 years. • The clinical presentation of roseola infantum often includes: Sudden onset of high fever, which can last for 3-5 days. • Children may become irritable, fussy, or lethargic during the fever phase
- 40. Rash • HHV-6 reactivationcan lead to; • Encephalitis: Inflammation of the brain, which can cause severe neurological symptoms such as headache, fever, confusion, seizures, and coma
- 41. • Pneumonitis: Inflammationof the lungs, leading to cough, shortness of breath, and difficulty breathing. • Retinitis: Inflammation of the retina, which can cause vision loss or blindness. • Gastroenteritis: Inflammation of the gastrointestinal tract, resulting in diarrhea, abdominal pain, and nausea.
- 42. • Bone marrowsuppression: HHV-6 reactivation can interfere with bone marrow function, leading to anaemia, neutropenia, and thrombocytopenia. • Diagnostic Methods and Treatments for HHV-6 and HHV-7 Infections • Blood tests:
- 43. • Blood tests: oPolymerase chain reaction (PCR): Detects the presence of HHV-6 or HHV-7 DNA in blood samples. o Serology: Measures antibodies against HHV-6 or HHV-7 in blood samples. • Cerebrospinal fluid (CSF) analysis: • PCR can be used to detect HHV-6 or HHV-7 DNA in CSF samples, particularly in cases of encephalitis.
- 44. • Tissue biopsy: Insome cases, a tissue biopsy may be necessary to confirm the diagnosis, especially if the virus is suspected to be causing disease in organs like the lungs or liver
- 45. • Treatments • Treatmentfor HHV-6 and HHV-7 infections often depends on the severity of the illness and the patient's immune status. • In most cases, the infections are self-limiting and do not require specific treatment. However, in immunocompromised individuals or those with severe symptoms, antiviral medications may be necessary.
- 46. • Antiviral medications: oGanciclovir o Foscarnet o Valacyclovir
- 47. • The generalmechanism of action (MOA) of antiviral drugs used in the management of human herpesviruses like HHV-6 and HHV-7 involves the inhibition of viral DNA replication. These drugs typically act by: • Inhibiting Viral DNA Polymerase: They target the viral DNA polymerase enzyme, which is essential for viral DNA replication. Without this, the virus cannot replicate its genetic material.
- 48. • Nucleoside Analogues:Many of these drugs are nucleoside analogues, which mimic the building blocks of viral DNA. Once incorporated into the viral DNA during replication, they cause premature chain termination. • Direct Enzyme Inhibition: Some drugs, like Foscarnet, directly inhibit viral enzymes such as DNA polymerase by blocking its functional sites, further preventing the virus from replicating. • These actions help control viral spread and reduce infection severity.
- 49. Ganciclovir • Ganciclovir, Inhibitsviral DNA synthesis by competing with deoxyguanosine triphosphate (dGTP), leading to premature DNA chain termination in herpes viruses.
- 50. Foscarnet • Foscarnet, Apyrophosphate analogue that directly inhibits viral DNA polymerase by binding to its pyrophosphate binding site, blocking DNA synthesis.
- 51. Valacyclovir • Valacyclovir, Aprodrug of acyclovir, it inhibits viral DNA polymerase after conversion to acyclovir triphosphate, preventing DNA replication.