Virusuri cu ARN Simetrie helicoidala Neinvelite : virusuri ale plantelor (tobacco mosaic virus) Invelite ORTHOMYXOVIRIDAE PARAMYXOVIRIDAE CORONAVIRIDAE

RHABDOVIRIDAE BUNYAVIRIDAE ARENAVIRIDAE FILOVIRIDAE Virusuri cu ARN Simetrie icosaedrica/cubica Neinvelite (fara anvelopa) PICORNAVIRIDAE CALICIVIRIDAE REOVIRIDAE Invelite (cu anvelopa) TOGAVIRIDAE FLAVIVIRIDAE RETROVIRIDAE

Virusuri cu ARN, simetrie helicoidala, invelite ORTHOMYXOVIRIDAE = V. gripale Afinitate pentru receptori mucoproteici Structura particulei virale: Portiune centrala = ribonucleoproteina (RNP) Invelis viral Influenza virus Virusuri cu ARN, simetrie helicoidala, invelite ORTHOMYXOVIRIDAE = V. gripale Portiune centrala = ribonucleoproteina (RNP) ARN ss : 8 segmente => permite reasortare genica intre genomuri virale diferite, prezente concomitent in aceesi celula => variatia antigenica Protomere (subunitati proteice atasate de ARN) Transcriptaza virala

Virusuri cu ARN, simetrie helicoidala, invelite ORTHOMYXOVIRIDAE = V. gripale Invelis viral Proteina M: asigura stabilitatea structurala Strat lipidic: lipide din membrana celulei infectate Peplomere = glicoproteine codificate de virus; 2 Proiectii: N = neuraminidaza si H= hemaglutinina Virusuri cu ARN, simetrie helicoidala, invelite ORTHOMYXOVIRIDAE Invelis viral H = hemaglutinina rol de atasare de celula, pe receptorii mucoproteici; se poate atasa si pe hematii => aglutinare; este antigenica => anticorpi neutralizanti, protectori, care inhiba atasarea v. pe celula si inhiba hemaglutinarea; exist 14 HA, din care H1, H2, H3 pot infecta omul Virusuri cu ARN, simetrie helicoidala, invelite ORTHOMYXOVIRIDAE Invelis viral N = neuroaminidaza scindeaza acidul neuraminic din mucoproteinele pe care se fixeaza; intervine in eliberarea v. din celulele infectate prin inmugurire; exist 9 N, din care N1, N2 pot infecta omul; este antigenica => anticorpi care impiedica eliberarea v. din celula => impiedica raspandirea virusului Virusuri cu ARN, simetrie helicoidala, invelite ORTHOMYXOVIRIDAE Antigenele virusurilor gripale Antigen intern = proteina M si ribonucleoproteina (RNP) Determina specificitatea de tip 3 tipuri antigenice: v. gripal A, B, C A - infecteaz omul i animale, psri => variabilitate antigenic mare datorat reasortrii tipurilor umane cu cele animale dac ajung s infecteze acelai organism => pandemii B => variabilitate antigenic mic, sporadic datorat mutaiilor C - relativ stabil antigenic Virusuri cu ARN, simetrie helicoidala, invelite ORTHOMYXOVIRIDAE Antigenele virusurilor gripale Antigene de invelis: N si H Confera specificitate de subtip si varianta In timp sufera modificari structurale si antigenice => variabilitate antigenica

Virusuri cu ARN, simetrie helicoidala, invelite ORTHOMYXOVIRIDAE Variatia antigenica a virusurilor gripale Variatii antigenice minore (antigenic drift) Variatii antigenice majore (antigenic shift) Virusuri cu ARN, simetrie helicoidala, invelite ORTHOMYXOVIRIDAE Variatia antigenica a virusurilor gripale Variatii antigenice minore (antigenic drift) se datoreaz acumulrii de mutaii punctiforme n genele care codific H sau N ;apar prin alunecareantigenica => pot conduce la o tulpin nou din punct de vedere antigenic doar dac 2 sau mai multe mutaii pot fi susinute.

Virusuri cu ARN, simetrie helicoidala, invelite ORTHOMYXOVIRIDAE Variatia antigenica a virusurilor gripale Variatii antigenice majore (antigenic shift) Datorit existenei celor 8 sgm de ARN, cnd o celul e coinfectat cu 2 tulpini diferite, aparinnd aceluiai tip (A) => amestec al segmentelor parentale => asamblate n virioni progeni = reasortare genic=>noi subtipuri virale => modificri brute ale Ag de suprafa = Ag. shift => izbucniri epidemice ale gripei, ridicnd probleme importante pentru vaccinare. Antigenic drift creates influenza viruses with slightly modified antigens, while antigenic shift generates viruses with entirely novel antigens. How antigenic shift, or reassortment, can result in novel and highly pathogenic strains of human influenza

The "Spanish flu", 19181919. First identified early in March 1918 in US troops training at Camp Funston, Kansas. By October 1918, it had spread to become a world-wide pandemic on all continents, and eventually infected 2.5 to 5% of the human population, with 20% or more of the world population suffering from the disease to some extent. Unusually deadly and virulent, it ended nearly as quickly as it began, vanishing completely within 18 months. In six months, some 50 million were dead; some estimates put the total of those killed worldwide at over twice that number.

An estimated 17 million died in India, 675,000 in the United States[21] and 200,000 in the UK. The virus was recently reconstructed by scientists at the CDC studying remains preserved by the Alaskan permafrost. They identified it as a type of H1N1 virus.

The "Asian Flu", 195758. An H2N2 caused about 70,000 deaths in the United States. First identified in China in late February 1957, the Asian flu spread to the United States by June 1957. The "Hong Kong Flu", 196869. An H3N2 caused about 34,000 deaths in the United States. This virus was first detected in Hong Kong in early 1968, and spread to the United States later that year. Influenza A (H3N2) viruses still circulate today. In the spring of 1918 large numbers of soldiers in the trenches in France became ill. The soldiers complained of a sore throat, headaches and a loss of appetite. Although it appeared to be highly infectious, recovery was rapid and doctors gave it the name of 'three-day fever'. At first doctors were unable to identify the illness but eventually they decided it was a new strain of influenza. The soldiers gave it the name Spanish Flu but there is no evidence that it really did originate from that country. In fact, in Spain they called it French Flu. Others claimed that the disease started in the Middle Eastern battlefields, whereas others blamed it on China and India. A recent study argued that the disease was brought to the Western Front by a group of USA soldiers from Kansas. Policemen in Seattle wearing masks made by the Red Cross, during the influenza epidemic. December 1918. March, 2005: Women carry a basket of chickens through Hanoi, Vietnam. A top Vietnamese health official blamed public ignorance about bird flu, weak surveillance systems, and smallscale farming activities for the re-emergence of the disease. Photo: Dept. of State Diagnostic de laborator

Spalaturile nazofaringiene sau aspiratul traheobronsic (la copii) sint probele recoltate pentru izolare. Optiunea pt un anumit substrat gazda (animal, om, culturi celulare) depinde de tipul si subtipul circulant. Daca acelasi subtip se izoleaza repetat este sigur cel prevalent. Identificarea se face serologic.

Diagnostic de laborator Tipul de virus gripal (A,B,C) se identifica prin reactia de fixare a complementului in raport cu antigenul nucleocapsidar. Subtipurile sint diagnosticate prin inhibitia hemaglutinarii. O modificare a ultimei reactii este testul de hemoliza radiala in care, in gel se incorporeaza antigenul, eritrocitele si complementul.

Daca serul contine anticorpi reactia pozitiva se vizualizeaza ca un inel hemolitic in jurul godeului cu ser. Diagnostic de laborator Diagnostic de laborator

Diagnosticul rapid in infectiile respiratorii acute se face in prezent prin imunoflorescenta.

Proba contine celule descuamate din tractul respirator iar antigenul este identificat cu baterii de seruri care includ seruri antigripale, antiparagripale, antiadenovirale, antireovirale etc.

Supravegherea serologica a colectivitatilor constituie o preocupare permanenta care poate alerta din timp asupra modificarilor antigenice ale virusurilor circulante. Tehnicile imunoenzimatice sint din ce in ce mai mult folosite in aceste actiuni.

Virusuri cu ARN, simetrie helicoidala, invelite ORTHOMYXOVIRIDAE Tratament Amantadina/Rimantadina = inhib ataarea de celulele gazd => trebuie luat foarte timpuriu Zanamivir, Oseltamivir = TAMIFLU - inhibitori de neuraminidaz sunt eficieni mai trziu n infecie Profilaxie Vaccin-ex. A/SOLOMON ISLANDS/2006 H1N1 A/WISCONSIN/2005/H3N2 B/MALAYSIA/2004 Programe de supraveghere antigripala Obiectivele : - depistarea precoce a puseelor epidemice si definirea agentului etiologic implicat; - izolarea de tulpini virale din focare epidemice si cazuri sporadice: studiul antigenic comparativ cu tulpinile recomandate pt productia de vaccin - estimarea impactului gripei asupra nivelelor de morbiditate si mortalitate - definirea grupelor de populatie expusa si cu risc crescut de aparitie a complicatiilor - actualizarea vaccinului gripal Virusuri cu ARN, simetrie helicoidala, invelite RHABDOVIRIDAE

gen Vessiculovirus v. stomatitei veziculare (VSV) gen Lyssavirus (gr. Lyssa = nebunie) v. rabic (v. rabic slbatic de strad) - serotip 1 v. rabice asociate

virus rabic Lagos de liliac - serotip 2, virus Mokola - serotip 3, virus Duvehange - serotip 4,

Contaminarea uman rabia este o zoonoza musctura animal bolnav de rabie Incubatia variaza intre 10 zile si peste 6 luni (in medie 3-8 saptamini) in functie de caracterele plagii muscate si specia animalului rabid transmiterea virusului prin aerosoli de la lilieci.

Transmiterea de la o persoan bolnav la o persoan sntoas prin saliv: rar, la personal medical, autopsieri, personal de laborator. transplant de cornee de la o persoan decedat, (cteva cazuri citate ).

Rabia (lat. rabiere = a fi violent) Rabia

Virusul se replica la nivelul plagii muscate, in celulele musculare striate, unde ramine cantonat in cursul incubatiei Virusul traverseaza jonctiunea neuromusculara si se propaga axonal, centripet, catre SNC, in maduva, apoi in creier unde se replica abundent Patogenez Virusul rabic este neurotrop si are afinitate speciala pt receptorul acetilcholinic din jonctiunea neuromusculara Alterarile morfologice determinate de replicarea virala intereseaza atit elementele presinaptice (nervoase) cit si cele postsinaptice (musculare) multiplicarea n SCN a virusului rabic encefalomielit degenerri neuronale cerebrale si medulare progreseaz descendent(centrifug) pe calea nervilor periferici spre glandele salivare, cornee, piele Diagnosticul de laborator

- este o urgenta Se refera in primul rind la dg. bolii la animalul banuit a fi rabid Diagnosticul se face prin: - examinarea creierului pt incluzii (dg. in citeva ore) - inocularea animalelor de lab (dg. in 4-21 zile) - dg. prin imunoflorescenta

Diagnosticul de laborator

La om:

- dg. in cursul bolii se poate face prin identificarea antigenului prin imunoflorescenta pe amprente corneene sau pe biopsii din mucoasa bucala sau din piele - dg. postmortem : evidentierea incluziilor Babes-Negri, izolare de la soarece, imunoflorescenta pe sectiuni de creier Virusul rabic corpusculi Babes Negri Vaccinarea uman

vaccin Pasteur (v. rabic fix): mduv uscat de iepure vaccin Semple: creier de iepure inactivat cu formol vaccin Fermi: creier de oaie inactivat cu propiolacton creier de soarece n. n DEV (duck embrio vaccine = culturi celulare de embrion de rat); HDCV = vaccin din celule umane diploide Vaccinarea animalor: - virus viu atenuat Flury (pe embrion de pasre)

Tratament i Profilaxie: ser antirabic; Ig antirabice umane vaccinare (5 doze) Arbovirusuri (arthropode borne viruses) virusuri transmise de artropode (nari, cpuse, flebotomi). vectori specifici si rezervoare animale prevalen sezonier si limitri geografice fac parte din familii diferite, au n comun modul de transmitere i bolile produse. Produc: - boli febrile cu artralgii, - encefalite, transmise prin nari sau prin cpuse - febre hemoragice, - evoluie grav, letal (encefalite, febre hemoragice). Clasificarea Arbovirusurilor

Familia Togaviridae : gen Alphavirus (Arbovirus grup A) Familia Flaviviridae genul Flavivirus Familia Bunyaviridae: genurile Bunyavirus, Hantavirus, Nairovirus i Phlebovirus Familia Arenaviridae - genul Arenavirus v.coriomeningitei limfocitare (rezervorul este reprezentat de roztoare)

Virusuri cu ARN, simetrie helicoidala, invelite BUNYAVIRIDAE

gen Bunyavirus: Virusuri transmise prin cpuse: v. encefalitelor de cpuse: v. encefalitelor de California v. encefalitei La Crosse

Virusuri cu ARN, simetrie helicoidala, invelite ARENAVIRIDAE

v. meningitei limfocitare: are ca si rezervor soarecele de cas (Mus musculus) meningit aseptic, sindrom asemntor gripei produc febre hemoragice sudamericane: argentiniene, boliviene.

Virusul meningitei limfocitare virus cu ARN din grupul Arenovirus rezervor: rozatoarele (soareci si hamsteri) infecteaz accidental omul, prin excreiile roztoarelor izbucniri epidemice meningite sau encefalite Evoluia clinic poate fi prelungit, bifazic rata recidivelor crescut. Virusuri cu ARN, simetrie helicoidala, invelite FILOVIRIDAE

v. Marburg

v. Ebola febre hemoragice africane Familia Flaviviridae Virusuri transmise prin nari: v encefalitelor de nar: encefalita japonez, encefalita Murray Valey, encefalita Saint Louis v. West Nile: meningit, encefalit Virusuri transmise prin cpue: v. encefalitelor de cpue encefalita rus de primvar - var; encefalita central european; encefalita scoian Familia Flaviviridae 1. Arbovirusuri grup B

Virusuri transmise prin nar: v. febrei galbene v. Denga denga: febr cu artralgii, mialgii, limfadenopatii si rash v encefalitelor de nar v. West Nile Virusuri transmise prin cpuse (v. encefalitelor de cpuse) 2. virusurile hepatitelor NU sunt arbovirusuri, NU sunt transmise prin vectori Hepacivirus: virusul hepatitei C (HCV): Hepatit C virusul hepatitei G (HGV): Hepatit G Familia Togaviridae: gen Alphavirus Virusuri transmise prin nar: v. encefalitelor ecvine de Vest (EEW), de Venezuela (EEV),

Togavirusuri - repartizare geografica Africa: arbovirusul de grup A (alfavirusurile) Chupungunya i Onyongin-yong, Caraibe, America Centrala si de Sud arbovirusul de grup B: febr galben Australia alfavirusurile Murray Hill si Roos River.

Virusuri cu ARN, simetrie icosaedrica, invelite RETROVIRIDAE - trei subfamilii sint grupate in fam. Retroviridae : - oncovirinae- respectiv, virusurile oncogene ARN la pasari, bovine. De la om in aceasta familie au fost incluse virusurile HTLV ( Human T-cell Leukemia Viruses I si II ) . HTLV I asociat cu leucemia/limfoamul cu celule T (boala endemica in Asia de Sud-Est, Japonia si zona Marii Caraibilor) si ulterior, cu alte entitati clinice: parapareza tropicala spastica, dermatita infectioasa jamaicana, polimiozite, artropatii. HTLV II izolat in sindroame hematologice rare ( leucemia cu celule paroase hairy cells leukemia). - lentivirinae agentii unor afectiuni lent degenerative ale SNC si virusul HIV - spumavirinae agenti ai unor infectii asimptomatice