Herpes Viruses PDF

‫ﺑﺳم ﷲ اﻟرﺣﻣن اﻟرﺣﯾم‬  Herpes Viruses By Sahar Taher Prof. of Medical Microbiology & Immunology Faculty of Medicine Mansoura & Horus University Contact us Sahar Taher E-mail: [email protected] [email protected] Mobile: 0100241750...

‫ﺑﺳم ﷲ اﻟرﺣﻣن اﻟرﺣﯾم‬  Herpes Viruses By Sahar Taher Prof. of Medical Microbiology & Immunology Faculty of Medicine Mansoura & Horus University Contact us Sahar Taher E-mail: [email protected] [email protected] Mobile: 01002417509 Academic hours: Saturday- Tuesday  Learning outcomes 1. Clarify the structure Herpes viruses. 2. Mention the classification & characters of Herpes viruses. 3. Differentiate between members of alpha, beta & gamma Herpes virus families regarding: Name of virus, method of transmission, primary infection, site of latency, reactivation. Lab. Diagnosis.  Prevention & treatment.  ILO-1 Herpes viruses structure  Virion: Icosahedral.  Genome: ds DNA, linear.  Envelope: with glycoprotein spikes.  ILO-2 Classification & Characters of Herpes Viruses Eight human herpes viruses are known. All have the ability to enter a latent state following primary infection and to be reactivated at a later time. Herpesviridae have been divided into three subfamilies: alpha, beta & gamma.  Classification of Herpesviruses Alpha herpesvirinae Beta herpesvirinae Gamma (Cytolytic) They have been divided into threeherpesvirinae (Cytomegalic) subfamilies: (Oncogenic) 1- Herpes simplex 5- Cytomegalovirus 4- Epstein-Barr virus virus type 1 (HSV-1 or (HHV-5) (HHV-4). HHV-1) 2- Herpes simplex 6- Human herpes 8- Kaposi's sarcoma- virus type 2 (HSV-2 or viruses type 6 associated herpes HHV-2) (HHV-6) virus (KSHV) or (HHV-8). 3- Varicella – Zoster 7- HHV-7. virus (VZV or HHV-3).  ILO-3 Alpha Herpesvirinae 1- Herpes simplex viruses There are 2 distinct herpes simplex viruses, type 1 and type 2. The two viruses cross-react serologically but some unique proteins exist for each type.  Transmission and pathogenesis HSV- 1 HSV- 2 Mode of Primarily in saliva by sexual contact transmission (kissing) Multiplies locally in the mucous membrane or a braded skin causing vesicular lesion. Site of lesion Mainly orofacial Genital lesions lesions However, both types of HSV can infect oral or genital mucosa depending on regions of contact.  Clinical syndromes HSV-1 HSV-2  Primary Acute Genital herpes infection gingivostomatitis. Neonatal Herpes libialis (cold infection sores Aseptic meningitis Herptic whitlow Keratoconjunctivitis, encephalitis. Disseminated infections in immuno- compromised.  Clinical syndromes HSV-1 HSV-2  Latency: Trigeminal ganglia. Sacral ganglia.  Reactivation: In response to stimuli as common colds, hormonal changes and sunlight. Cold sores. Occur more Keratitis. frequently. Often asymptomatic but still results in viral shedding.  Diagnosis of HSV-1& 2 Detection of viral particles by E.M. Histological staining (Giemsa stain) of scrapings or swabs from lesions to detect intranuclear inclusion bodies. Virus isolation from herpetic lesions. Serologic diagnosis.  Prevention & treatment No available vaccine. Acyclovir is the treatment of choice. It shortens the duration of the lesion and decreases shedding of the virus. No drug treatment prevents recurrences. No effect on the latent state.  2- Varicella-Zoster virus A- Primary infection:  Varicella or chicken pox vesicular rash which starts on the trunk and spreads to the limbs and face. B- Latency:  Dorsal root ganglion causing shingles.  characters Chicken pox (varicella) Shingles (Zoster) Definition Contagious disease causes by Infection of nerve and infection with varicella-zoster virus skin around them, caused by reactivation of Varicella-zoster virus Age of the All ages are susceptible but, much Occur in adults patient more common in children Transmission by droplets and by direct contact latent virus in the nerve with the lesions ganglia of the body. Under certain conditions, the virus is activated and the shingles is induced. Type of the Primary infection Reactivation of old infection infection  characters Chicken pox (varicella) Shingles (Zoster) Symptoms Fever, itching rash starts on the The shingles proceed trunk and spreads to the limbs with sever pain and rash. and face. The rash affects a skin Vesicles appear& lesions of area innervated from a different stages are present particular peripheral together. nerve Rash Itching Painful Non grouped vesicles. Grouped vesicles Complications Rare as meningitis, encephalitis More often and pneumonia. Primary varicella: Shows multiple stages of vesicles, papules, and crusted lesions on the abdomen. Zoster (shingles)— Diagnosis: Mainly clinically. But, laboratory diagnosis can be done as on the same line used for HSV. Treatment: Systemic disease in immunocompromised patients can be treated with acyclovir. Prevention: VZV vaccine: a live attenuated vaccine, one dose is recommended for children 1 to 12 years of age. It prevents varicella, but zoster still occurs in those previously infected because the vaccine does not eliminate the latent state.  ILO-3 Beta Herpesvirinae 1- Cytomegalovirus (CMV) HHV-5 2- HHV-6 3- HHV-7  Cytomegalovirus (CMV) Transmission and pathogenesis: Early in life: transmitted transplacentally, within birth canal and commonly in breast milk. Later in life: it is transmitted via saliva (most common route), sexually, by blood transfusion and organ transplants. Clinical significance: A- Primary infection: 1- In healthy individuals:  Asymptomatic infection  Infectious mononucleosis-like syndrome. 2- Infection of immunodeficient patients: hepatitis and pneumonia are common. In AIDS patients, diarrhea and retinitis may also occur. 3- Congenital infection:  CMV is the most common intrauterine viral infection  In-utero it causes abortion or still birth. B- Latency and reactivation  In monocytes, macrophages and kidney. Lab. Diagnosis: Virus isolation in cell culture, CPE in Owls eye the form of typical swollen and translucent cells with intra nuclear inclusion bodies. The inclusion bodies are intranuclear and have an oval “owls eye” shape. PCR for detection of CMV nucleic acid in tissues or body fluids e.g. CSF. Treatment: Ganciclovir is effective for treatment of retinitis and pneumonia in AIDS patients  Human Herpes viruses 6 and 7 The two variants of HHV-6 (HHV-6A and HHV-6B) and HHV-7, are members of the genus Roseolovirus of the subfamily Betaherpesvirinae. HHV-6B and HHV-7 cause a common disease of children, exanthem subitum commonly known as roseola (macular rash on neck and trunk and spare face). HHV-7 was isolated in a similar manner from the T cells of a patient with AIDS who was also infected with HHV-6.  ILO-3 Gamma Herpesvirinae 1- Epstein Barr Virus (EBV) HHV-4 2- HHV-8  Epstein-Barr virus (EBV)  Transmission and pathogenesis: By intimate contact with infected saliva. Viral replication occur in the oropharyngeal epithelium, following which some of the progeny virus infect B lymphocytes  polyclonal B cell proliferation and non specific ↑ of IgM (heterophile antibodies that aggregate sheep and horse RBCs), IgG and IgA. Infected B cells are rejected by cytotoxic T cells which change in morphology and appear as atypical T lymphocytes in the peripheral blood.  Clinical significance: 1. Infectious mononucleosis: characterized by fever, headache, malaise, pharyngitis, lymphadenopathy and increased levels of liver enzymes in the blood. It lasts several weeks and complete recovery may take much longer. 2. EBV and malignancies:  Burkitt’s lymphoma: It is a unique malignancy of the jaw in African children.  Nasopharyngheal carcinoma: common among Chinese  Oral hairy leukoplakia: benign lesion of the tongue 3. Latency and reactivation:  EBV remains latent in B cells, reactivation results in initiation of the viral lytic cycle. Hairy leukoplakia—note whitish plaques on lateral aspect of tongue caused by Epstein–Barr virus.  Laboratory diagnosis: 1. Blood smear: to detect lymphocytosis and 30% abnormal lymphocytes. 2. DNA hybridization: Detection of EBV in patient’s peripheral lymphocytes. 3. Detection of heterophile antibodies: which agglutinate sheep erythocytes (paul-Bunnel test). It is non specific test. 4. Detection of EBV specific Abs: to viral capsid antigen or EBV nuclear antigen by ELISA. 5. Virus isolation from saliva is difficult.  Treatment: No drug available to treat EBV. Vaccine is being developed.  Human Herpes virus 8(HHV- 8) Also called Kaposi sarcoma associated herpes virus. Kaposi sarcoma is one of the characteristic opportunistic diseases associated with AIDS. Kaposi sarcoma is a rare type of B-cell lymphoma. Similar to EBV, the B cell is the primary target cell for HHV-8. Kaposi’s sarcoma—note several dark purple lesions on the foot caused by human herpesvirus 8 (Kaposi’s sarcoma–associated virus).  KEY CONCLUSIONS There are eight human herpesviruses causing a range of diseases including cold sores and genital sores, chicken pox and shingles, mononucleosis, roseola, congenital blindness, lymphomas, and Kaposi sarcoma. All herpes viruses establish lifelong latent infections. There are drugs that can lessen the severity of diseases caused by lytic replication of herpesviruses but there is no treatment for latent infections. There is an effective vaccine for VZV that prevents chicken pox and a higher dose version for the elderly that lessens the incidence of zoster. The γ-herpesviruses can cause cancers including Burkitt lymphoma, other B-cell lymphomas, and Kaposi sarcoma.  Questions 1. Vaccines have been 2. Which of the following is demonstrated to be the most common cause of efficacious in preventing congenital viral infection? herpes virus disease in a. Varicella-zoster virus which one of the following b. Herpes simplex virus type situations? 2 a. HSV-1 primary infection c. Human herpes virus 8 b. Varicella-zoster infection d. Cytomegalovirus c. HSV-2 reactivation e. Human herpes virus 6 d. CMV primary infection c. EBV reactivation  References or further readings Brooks, G. F., Jawetz, E., Melnick, J. L., & Adelberg, E. A. (2019). Jawetz, Melnick, & Adelberg's medical microbiology. New York: McGraw Hill Medical. Lippincott’s Illustrated Reviews: Microbiology third edition (2013).