1. 약품미생물학 생명산업과학대학 생물환경학과 김정호 http://bioenv.sunchon.ac.kr

2.  Adenoviridae  Papovaviridae  Parvoviridae  Herpesviridae  Poxviridae DNA Viruses

3.  Family Adenoviridae Group I : ds DNA Nonenveloped, icosahedral nucleocapsid Initially isolated from human adenoid ( 인두편도 ) 7 Human adenovirus species (A to G) : Genus Mastadenovirus 57 accepted human adenovirus types (HAdV-1 to 57) Respiratory disease (mainly species HAdV-B & C) Acute respiratory disease (ARD, 급성 호흡기 질환 ) Conjunctivitis (HAdV-B and D) Epidemic keratoconjunctivitis ( 유행성 각결막염 ) Pharyngoconjunctival fever (HAdV-B, 비인두결막염 ) Conjunctivitis + Respiratory disease Gastroenteritis (HAdV-F types 40, 41, HAdV-G type 52) Adenoviridae

4. Transm ission : respiratory droplets, fecal-oral routes Application Viral vector for gene therapy : cystic fibrosis ( 낭포성 섬유증 ) affect both replicating and non-replicating cells accommodate large transgenes code for proteins w/o integrating into the host cell genome Delivery platform for foreign antigens to human MDC MDC (myeloid dendritic cell) Oncolytic adenovirus : cancer treatment (China) Adenoviridae

5.  Family Papovaviridae Pa, papillomavirus; Po, polyomavirus; Va, ‘vacuolating’ virus (simian vacuolating virus 40, SV40, now known to be part of the polyomavirus genus) ds DNA, icosahedral, no envelope Recently split into Papillomaviridae & Polyomaviridae Associated with various neoplasms in mammals Human papillomavirus (HPV, 인유두종바이러스 ) Human polyomavirus Papovaviridae

6.  Family Papillomaviridae Latin ‘pappilla’ ( 유두 ) + Greek ‘oma’ (tumor) Human papillomavirus (HPV, 인유두종 바이러스 ) transmitted thru sexual contact infect the an genital region HPV infection HPV is the most common STI in adults, worldwide Subclinical (asymptomatic) infection : Small benign tumor : papillomas or warts, HPV6 or HPV11 Ano-Genital warts : HPV6 or HPV11, condyloma Benign head and neck tumor ( 양성 두경부 종양 ) : HPV6 or HPV11 oral pappiloma, laryngeal pappiloma Cancer : cervix, vulva, vagina, penis, oropharynx, anus HPV16 and 18 Human paillomavirus

7. Diagnosis Papanicolaou (Pap) test : Pap smear Cervical intraepithelial neoplasia (CIN, 자궁경부상피이형성증 ) precursor to cervical cancer HPV vaccines Gardasil : HPV-16, HPV-18, HPV-6, HPV-11 Cervarix : HPV-16 & HPV-18 Gardasil 9 : December 2014, approved by USA (HPV-6, HPV-11, HPV-16, HPV-18) + (HPV-31, HPV-33, HPV-45, HPV-52, and HPV-58)

8.  Family Polyomaviridae ds DNA, icosahedral, non-enveloped potentially oncogenic polyoma : multiple (poly-) tumors (-oma) Human polyomavirus JC virus : Progressive multifocal leukoencephalopathy ( 진행성 다소성 백질뇌염 ) BK virus : nephropathy Simian vacuolating virus 40 (Simian virus 40, SV40) human, monkey cancer? Human polyomavirus

9.  Family Parvoviridae Group II : linear, non-segmented ssDNA viruse Average genome size of 5000 nucleotides Non-enveloped Latin ‘parvum’ meaning ‘small’  Parvovirus B19 Discovered in well B19 of a large series of microtiter plates B19 virus, Erythrovirus B19 Genus : Erythrovirus Primate erythroparvovirus 1 Childhood rash : fifth disease (erythema infectiosum or slapped cheek syndrome) Hurmoral & Cell-mediated immunity Vaccine available : inactivated & attenuated Parvoviridae

10.  Family Herpesviridae Group I, ds DNA virus, icosahedral, enveloped Greek herpein ("to creep") refer to the latent, recurring infection can cause latent or lytic infections Herpes simplex virus (HSV) 단순헤르페스 바이러스 HSV-1, HSV-2 : orolabial herpes ( 구순포진 ), genital herpes Varicella zoster virus (VZV) 수두 대상포진 chicken-pox ( 수두 ), shingles ( 대상포진 ) Human cytomegalovirus (HCMV) 사람 거대세포 바이러스 Epstein-Barr virus (EBV) 엡스타인바 바이러스 mononucleosis ( 단구핵증 ) All herpesviruses share a characteristic ability to remain latent within the body over long periods. More than 90% of adults have been infected with at least one of these, and a latent form of the virus remains in most people. Herpesviridae

11.  단순헤르페스 바이러스 Family : Herpesviridae, Subfamily : Alphaherpesvirinae Genus : Simplexvirus Species : Herpes simplex virus 1 & 2 (HSV-1 & HSV-2) Human herpesvirus 1 & 2 (HHV-1 & HHV-2) HSV-1 : cold sore (fever blisters, herpes labiales) ( 구순포진 ) HSV-2 : genital herpes ( 생식기 헤르페스 ) Ubiquitous & contagious Neurotropic & neuroinvasive persist in the body by becoming latent and hiding from the immune system in the cell bodies of neurons virus in a nerve cell becomes active and is transported via the neuron's axon to the skin, where virus replication and shedding occur and cause new sores ) Herpes simplex virus (HSV)

12.  HSV-1 infection Primary infection : blisters Recurrent disease Cold sores (fever blisters 열성물집, herpes labialis 구순포진 ) Herpes Gingivostomatitis ( 치육구내염 ) lips, mouth & gums lesions heal with a scab characteristic of herpetic disease Virus travels to trigeminal nerve ganglion (3 차 신경절 ) Latent state : for the life time of the infected person Reactivation of virus : stressful stimuli virus (thru peripheral nerve) to lips or other parts of face Herpetic whitlow : hand Herpetic keratitis (inflammation of the cornea, 각막결막염 ) a major cause of blindness Herpes viral Encephalitis : inflammation on temporal lobe ( 측두엽 ) can be fatal, 신경성 후유증 HSV

13.  Herpes genitalis (Genital Herpes) HSV-2 & HSV-1 Transmitted by sexual contact Introduction into a break in a skin or mucous membranes Infection of epitherial cells : external genitalia, urethra, cervix Clusters of inflamed papules and vesicles The most common STI by the number of cases HIV-2 associated with a higher-than-normal rate of cervical cancer and miscarriages. Genital Herpes

14.  Neonatal (Congenital) herpes Vertical transmission of HSV from mother to newborn infected mother : caesarean section recommended Rare but serious : death, nerological symptoms, blindness SEM (skin, eye, mouth) herpes localized herpes) associated with trauma or surgery (including circumcision) DIS (disseminated) herpes affects internal organs, particularly the liver CNS (central nervous system) herpes  Herpes simplex virus is considered as a potential therapy for cancer and has been extensively clinically tested to assess its oncolytic (cancer killing) ability. Interim overall survival data from Amgen's phase 3 trial of a genetically- attenuated herpes virus suggests efficacy against melanoma. HSV

15.  Treatment Cannot be cured Acyclovir(ACV, Zovirax) Herpes virus, varicella zoster virus, Epstein–Barr virus Reduce the pain and the number of lesions in the initial case of genital herpes Decrease the frequency and severity of recurrent infections Valacyclovir (Valyl ester of ACV, Valtrex) Penciclovir Famciclovir (derivative of Penciclovir, Famvir) ACVs : Must be phosphorylated for antivral activity : by viral thymidine kinase Vidarabine (Vira-A, adenosine arabinoside, Ara A) Idoxuridine (iododeoxyuridine) Trifluridine HSV

16.  수두대상포진 바이러스 Family : Herpesviridae, Subfamily : Alphaherpesvirinae Genus : Varicellovirus Species Human herpesvirus 3 (HHV-3) Varicella zoster virus (VZV) Chickenpox (varicella, 수두 ) Herpes zoster (shingles, 대상포진 ) VZV infects the nerves After primary infection (chickenpox), VZV goes dormant in the nerves Can reactivate to cause a number of neurologic condition (shingles) Varicella zoster virus (VZV)

17.  수두 (Chickenpox, varicella) Caused by the initial infection with VZV Highly contagious Transmission Air-borne : coughs and sneezes of an infected person) Contact with blisters (Those with shingles may spread chickenpox) 1~2 days before rash appears ~ all lesions have crusted over Incubation period : 10 days ~ 3 weeks Symptoms characteristic skin rash that forms small, itchy blisters (face, chest, and back and then to the rest of the body) fever, feeling tired, and headaches. usually last five to ten days. Complications : pneumonia, inflammation of brain, bacterial infections of the skin People usually only get the disease once

18.  Chickenpox (varicella) Diagnosis : Symptom PCR : blister fluid, scabs Testing for antibody Varicella vaccine : Varivax : for children Effective for over 10 years in preventing varicella A second dose of vaccine recommended before school entry Treatment : calamine lotion to help with itching paracetamol (acetaminophen) to help with fevers antiviral medication (aciclovir) : for complications

19.  대상포진 (Herpes zoster, zoster, shingles, zona) Many years after the initial infection with VZV (chickenpox) Painful skin rash with blisters in a limited area on one side of the body (left or right), often in a stripe Rash usually heals within 2 ~ 4 weeks Postherpetic neuralgia : rarely residual nerve pain for months or years Vaccine : Zostavax (for older adults) Treatment Antiviral drug : famciclovir, valaciclovir Ig : zoster-immune globulin (ZIG), VZV immune globulin

20.  사람 거대세포 바이러스 Family : Hepesviridae, Subfamily : Betaherpesvirinae, Genus : Cytomegalovirus Species : Human cytomegalovirus (HCMV, CMV) Human hepesvirus-5 (HHV-5) Cytomegalo : 감염시 세포가 서로 융합하여 거대세포 형성 Widespread infection Typically unnoticed in healthy people Frequently associated with the salivary glands Remains latent within the body throughout life and can be reactivated at any time Human cytomegalovirus (HCMV)

21. Congenital infection The most frequently transmitted virus to a developing fetus Deafness, Learning disabilities, Mental retardation Cytomegalic inclusion disease ( 거대세포 봉입체병 ) Infection of the immunocompromised HIV-infected persons, organ transplant recipients Interstitial pneumonia ( 간질성 폐렴 ), Retinitis ( 망막염 ), Enteritis ( 장염 ) Can be life-threatening Treatment : rarely used due to high toxicity Ganciclovir, vilgancidlorvir, cidofovir, foscarnet Human cytomegalovirus (HCMV)

22.  Epstein-Barr virus (EBV) Human herpesvirus 4 (HHV-4) Family : Herpesviridae, Subfamily : Gammaherpesvirinae, Genus : Lymphocryptovirus, Species : Epstein-Barr virus Infects B cells of the immune system & epithelial cells Oral transfer of saliva and genital secretions Once EBV's initial lytic infection is brought under control, EBV latently persists in B cells for the rest of life Infections usually cause no or mild symptoms Most people become infected & gain adaptive immunity Infectious mononucleosis (IM) 전염성 단핵구증 Mono, glandular fever, Pfeiffer's disease, Kissing disease Fever, Sore throat, Fatigue Lymphadenopathy, Splenomegaly, Exudative pharyngitis ( 림프절 증대 ) ( 비장비대 ) ( 삼출성 인두염 ) Generally self-limiting, little treatment required Epstein–Barr virus (EBV)

23. Chronic disease : 만성질환 Periodically recurring disease chronic fatigue, fever, headache, pharyngitis Lymphoproliferative disease : 림프증식성 질환 particular forms of cancer Burkitt's lymphoma, Hodgkin's lymphoma, nasopharyngeal carcinoma Conditions associated with HIV : hairy leukoplakia ( 구강 백반증 ) central nervous system lymphomas No treatment, No vaccine available Evidence that infection with EBV is associated with a higher risk of certain autoimmune diseases, especially dermatomyositis, systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, and multiple sclerosis. Epstein–Barr virus (EBV)

24.  Poxviridae Group I : dsDNA 복제의 모든 과정이 세포질에서 일어남 Four genera of poxviruses may infect humans Orthopoxvirus : smallpox virus (variola, 천연두 ), vaccinia virus, cowpox virus, monkeypox virus Molluscipoxvirus : molluscum contagiosum virus (MCV, 전염성 연속종 ) Parapoxvirus : orf virus, pseudocowpox virus, bovine papular stomatitis virus Yatapoxvirus : tanapox virus, yaba monkey tumor virus Poxviridae

25.  Small pox (Red plague, Variola) Caused by Variola major or Variola minor Latin : Variola or Variola vera varius (spotted) or varus (pimple) Vaccination India : 1,000 BC China : late 10th C, widely practiced by the 16th century 1796, Edward Jenner, England, cowpox vaccine from vacca (Latin for cow) 19 th Century, vaccinia virus used 20 th Century : estimated 300–500 million deaths 1967 : 15 million infected, 2 million died. The last naturally occurring case of smallpox (Variola minor) was diagnosed on 26 October 1977. WHO certified the eradication of smallpox in 1979. Agent for bioterrorism Smallpox