Retro viruses (Slow viruses)

# ISBN 965-490-008-4

Sulkin & Pike VEEVenezuelanEquine Encephalitis

Skinhoj CDC NADC QQ

Q Fever Down the Drain Q Q Q Q

Collins

Phillips

Reitman & Wedum

X X X X X X X X X X X X X X X X X X

Andersen Cascade Impactor

Martin

Oncogenic or Slow Viruses

Encephalitis LCM Marburg Herpes B (Hepatitis Gemalaya Hantan

Herpes B-virus LCM Marburg NDV Parainfluenza Reovirus (type 3) Rabies Antrax Brucella Diplococcus pneumonia E, coli Tularemia Listeria Mycotacterium Pasteurella multocida

Pasteurella pneumotropica Pseudomonas aeroginosa Q Fever Salmonella Shigella Staphylococcus Streptococcus Yersinia pestis Y. psuedotuberculosis

Voororst

SPF Staphylcoccus Pasteurella Huebner NIAID

up scaling

Simian viruses C C C C in vivo EBV

Infectious mononucleosis

C B Papilloma moderate Species barrier SA

DNA Marek s Polyoma Adenovirus Herpes Papilloma Shope fibroma Shope papilloma Shope lymphoma SV40 RNA Rous sarcoma Leucosis CELO Leukemia Sarcoma Mamary tumor Leukemia Graffi Leukemia Leukemia Sarcoma mast cells DNA Herpes virus saimirii Herpes virus ateles Yaba pox EBV Nondefective adeno SV hybrid RNA Feline leukemia Feline sarcoma Wooly monkey fibrosarcoma Gibbon ape lymphosarcoma

Slow viruses Retro viruses LCMlymphocytic choriomeningitislcm LCM LCM LCM LCM Huebner LCM LCM

Transmissible Spongiform Encephalopathy CJD Dimentia Kuru & Creutzfeldt-Jacoob Benefit-risk Benefit-cost Cost-effectiveness

CB B B HIV B CDC

HIV Western BlotEIA HIV CB

E coil K-12 HV Host VectorEK1 EK2 EK3 BL4 BL1 Szybalski

DNA toxins WR Vesicular stomatitis virusvsvn G 3x10 4 pfu/0.05 ml VSVN

NIHJ. Rivkin Environmental Impact Statement

Retro CDC

Wedum & Kruse A A Q VEE

freeze drying lyophilization

Biosafety level 2 up scaling Kletz

Hazard and operability study - HAZOP Hazard analysis = HAZAN

Fisher Lincoln et al Batch

containment

National Institute of HealthNIHCenter for Disease ControlCDC (Good Laboratory Practices) GLP GLP

GLP GLP Federal Register (Good Manufacturing Practices) GMP GMP GMP GMP SOP - Standard Operation Procedures SOP SOP

(Code of Practice) COP GMP GLP COP

HEPA UV Air lock HEPA

Goggles

I II II PDF

III HEPA ή% I 1x 10-5 cc/sec at 2 w.g.*** pressure AII BII 1x10-5 cc/sec at 3 w.g. pressure III nnoή n/noή.w.g

II I BII AII III III

DNA II

HEPA UV

DOP Di Octyl PhtalateDOP HEPA

DOP HEPA HEPA HEPA HEPA

HEPA HEPA A B C III III HEPA

Host Vector HV-2HV-1 HV-1 E. Coli K-12 COL E1,pSC101 EK1 HV-2 EK2 DNA PFU

BL-3 HV-3 HV-1 HV2 HV2 BL2 BL4 BL3 BL3 BL3 BL3 BL3/HV2 HV1 HV2 BL3 BL2 BL3 BL3 BL3 BL3 BL3/HV1 HV1 HV2 BL4 BL3 BL4 BL4 BL4 BL4 BL4/HV1

TD MMR HBVB

B anti-hbs miu/ml anti-hbc HBsAg NIH P4P1protectionP P1 P2 P4P3

BSLBiosafety levelbl NIHCDC CDC NIH NCI CDC NIH WHO - BL1 P1 I C BL4 P2 II B BL3 P3 III A BL2 P4 IV BL1

III I II challenge Air lock

cfm fpm III HEPA interlock

BL III

HEPA HEPA HEPA

HEPA II I HEPA HEPA

CDC NIH www.cdc.gov.od/ohs/biosafty/bmbl 5/bmbl 5toc.htm

HEPA HEPA Liberman C C C C

Biosecurity

BL3 BL3 GLP, GMP

BL3 BL3 BL2 BL2 BL3 BL BL3

=Pounds per square inchpsi C

Gravity displacement HEPA C PSI

C C C C C

Bacillus stearothermophilus C C C

Bacillus subtilis C varniger B. subtilis C C

PPM 2CaOCl Na 2 S 2 O 2

b a d CO٢c c d c d 30 60 37 23 30 30 60 60 3 g/ft 3 8%-0.2% 2% 23-8 g/ft 3 b 85%-70% b b 85%-70% 30 30 5%-1% 500 ppm a 1600-25 ppm a 10 2%-0.1% C

C C w/v C

HEPA HEPA Hz

Infectious agent Contagious agent RetrovirusesRNA Slow viruses Arbo viruses Containment

High Efficiency Particulate Air HEPA Biological safety cabinet Glove box Safety cage

UV BL 1-4 = P 1-4 Biosafety levelbl ProtectionP NIH- EK 1-3 = HV 1-3 Host VectorHV;E. coli KEK - Plaque forming units PFU Up scaling Center for DiseaseCDC National Institutes of Health NIH Enzyme Immuno AssayAIE

Hazard Operability Study; Hazard-Analysis HAZOP ;HAZAN (Good Laboratory Practices) GLP (Good Manufacturing Practices) GMP Standard Operation Procedures SOP Code of PracticeCOP -Cubic feet per minutecfm -Feet per minutefpm

- V X G

הגורם Acinetobacter calcoaceticus 2 Actinobacillus actinoides Actinobacillus lignieresii 2 Actinobacillus suis 2 2 Actinomyces bovis 2 2 Actinomyces israelli 2 Aeromonas hydropphila 2 Araachnia propionica 2 2 Arizona hinshawii 2 2 Bacillus anthracis (v) 2 3 Bacillus cereus 1 1 Bacillus subtilis 2 2 Bacteroldes spp 2 Bartonella bacilliformis Bordetella bronchiseptica 2 Bordetella pertussis 2 3 Borrelia all spp 2 3 Brucella abortus 3 3 Brucella canis 3 3 Brucella melitensis 3 3 Brucella ovis 3 3 Brucella suis 3 Campylobacter fetus - subspecies fetus 3 Subspecies jejuni Subspecies intestinalis Chlamydia psittaci Chlamydia trachomatis Clostridium botulinum (v) Clostridium chauvoei Clostridium difficile Clostridium haemolyticum

Clostridium histolyticum Clostridium novyi Clostridium perfringens Clostridium septicum Clostridium sordellii Clostridium tetani (v) Corynebacterium bovis Corynebacterium diophtheriae Corynebacterium equi Corynebacterium ovis/pseudotuberculosis Corynebacterium ulcerans Corynebacterium haemolyticum Corynebacterium pyogenes Corynebacterium renale Edwardsiella tarda Enterobacter aerogenes Erysipelothrix insidosa Escherichia coli Escherichia coli, K 12 strain Francisella novicida Francisella tularensis Haemophilus ducreyi Haemophilus gallinarum Haemophilus haemolyticus Haemophilus influenzae Haemophilus parahaemolyticus Klebsiella pneumoniae Lactobacillus acidophilus Lactobacillus bulgaricus Lactobacillus casei Legionella pneumophila Legionella-like organisms Leptospira interrogans all serovars Listeria monocytogenes Mima polymorpha

Moraxella lacunata Moraxella osloensis Mycobacterium africanum Mycobacterium avium intracellulare Mycobacterium bovis Mycobacterium bovis (BCG strain) Mycobacterium chelonei Mycobacterium fortuitum Mycobacterium kansasii Mycobacterium leprae (G) Mycobacterium marinum Mycobacterium scrofulaceum Mycobacterium simiae Mycobacterium szulgei Mycobacterium tuberculosis Mycobacterium ulcerans (G) Mycobacterium xenopi Mycoplasma pneumoniae Neisseria gonorrhoeae Neisseria meningitldis Nocardia asteroldes Nocardia brasillensis Pasteurella haemolytica Pasteurella muftocida Pasteurella pneumotropica Plesiomonas shigelloides Proteus spp Pseudomonas aeroginosa Pseudomonas mallel (x) Pseudomonas pseudomallel Rickettsial Agents Coxiella burneti (v) Rickettsia akari Rickettsia canada Rickettsia conori Rickettsia montana

Rickettsia mooseri Rickettsia prowazeki (v) Rickettsia rickettsii (v) Rickettsia sennetsu Rickettsia tsutsugamushi Rochalima quintana Vole rickettsia Salmonella choleraesuis Salmonella entaritidis all serotypes Salmonella typhi (v) Serratia marcescens Shigella boydii Shigella dysenteriae Shigella flexneri Shigella sonnei Sphaerophorus necrophorus Staphylococcus aureus Staphylococcus epidermidis Streptobacillus moniliformis Streptococcus agalactiae Streptococcus pneumoniae Streptococcus pyogenes Treponema pailldum Treponema pertenue Vibrio cholerae (v) Vibrio parahaemolyticus Vibrio vulnificus Yersinia enterocolitica Yersinia pestis (v) Yersinia pseudotuberculosis

Absidia spp Aspergillus spp Blastomyces dermatitidis Candida spp Cladosporium trichoides Coccidioides immitis Cryptoccoccus neoformans Dermatophilus congolensis Epidermophyton spp Geotrichum spp Histoplasma capsulatum Histoplasma farciminosum (x) Loboa lobol Madurella mycetomi Microsporum spp Mucor spp Paracoccidioides brazilensis Rhizopus spp Sporothrix schenkii Trichophyton spp Trichosporon spp

Acanthocheilonema spp 2 2 2 Acanthamoeba spp 2 2 2 Ancylostoma spp 2 2 2 Angiostrongyius spp 2 2 2 Ascaris spp 2 2 2 Babesia spp 2 2 2 Balantldium spp 2 2 2 Brugia spp 2 2 2 Capillaria spp 2 2 2 Clonorchis spp 2 2 2 Cysticerus spp 2 2 2 Dicrocoelium spp 2 2 2 Dipetalonema spp 2 2 2 Diphylobothrium spp 2 2 2 Dipylidium spp 2 2 2 Dracunculus spp 2 2 2 Echinoccoccus spp 2 2 2 Entamoeba histolytica 2 2 2 Enterobius spp 2 2 2 Fasciola spp 2 2 2 Fasciolopsis spp 2 2 2 Giardia spp 2 2 2 Hymenolepsis spp 2 2 2 Heterophyes spp 2 2 2 Isospora spp 2 2 2 Leishmania spp (G) 2 2 2 Linguatula spp 2 2 2 Loa spp 2 2 2 Macracanthorhynchus spp 2 2 2 Necator spp 2 2 2 Naegleria fowleri 2 3 2

Naegleria gruberi 1 1 1 Onchocerca spp 2 2 2 Opisthorchis spp 2 2 2 Paragonimus spp 2 2 2 Plasmodium spp 2 2 2 Pneumocystis carinii 2 2 2 Schistosoma spp (G) 2 2 2 Strongyioides spp 2 2 2 Taenia spp 2 2 2 Toxascaris spp 2 2 2 Toxocara spp 2 2 2 Toxoplasma spp 2 2 2 Trichinella spp 2 2 2 Trichomonas vaginalis 2 2 2 Trichostrongylus spp 2 2 2 Trichuris trichiura 2 2 2 Trypanosoma spp (G) 2 2 2 Wuchereria spp 2 2 2

Adenoviruses (human) 3 Arenaviruses Lymphocytic choriomeningitis Viscerotrophic strains 2 3 3 Neurotrophic strains 3 3 3 Coronaviruses 2 2 2 Herpesvirus Group Herpesvirus hominis 2 3 2 Cytomegalovirus 2 3 2 Epstein-Barr virus 2 3 2 Herpesvirus simiae 4 4 4 Pseudo-rabies virus 2 3 2 Varicella virus 2 3 2 Myxo-Paramyxoviruses Canine distemper virus Canine distemper Virus (Snyder-Hill strain) 1 1 1 Influenza viruses (excluding pandemic strains) 2 3 2 Measles virus (v) 2 2 2 Mumps virus (v) 2 2 2 Newcastle disease virus 2 3 2 Parainfluenza viruses (human isolates) 2 3 2 Respiratorysyncitial virus 2 3 2 Subsclerosing Panencephalitis virus 3 2 Picomaviruses Coxsackie viruses Echoviruses

Poliomyelitis virus (wild) (v) Poliomyelitis virus (attenutated) (v) Rhinoviruses (human) 2 2 2 Poxviruses Cowpox virus 2 3 2 Molluscum contagiousum virus 2 3 2 Monkeypox virus (v) 3 4 3 Orf virus 2 3 2 Paravaccinia virus 2 3 2 Tanapox virus 2 3 2 Vaccinia virus (v) 2 3 2 Variola major virus restricted RESTR ICTED Variola minor virus restricted RESTR ICTED Whitepox virus restricted RESTR ICTED Yabapox virus 2 3 2 Papovaviruses SV 40 virus 2 3 2 B-K virus 2 3 2 Spongiform Encephalopathy Prions Creutzfeldt-Jacob agent (G) 2 3 3 Kuru agent (G) 2 3 3 Rotaviruses Togaviruses Rubella virus (v) 2 2 2 Ungrouped Agents Fifth Disease Agent 2 3 2 Hepatitis viruses (G) 2 3 2 Norwalk agent 2 3 2 Human Immunomodefeciency Virus (HIV) 2 3 2

Absettarov 4 4 4 Aino 3 3 3 Akabane 3 3 3 Araguari 3 3 3 Batama 3 3 3 Batken 3 3 3 Bhanja 3 3 3 Bimbo 3 3 3 Bluetongue-indigenous 2 3 2 Bluetongue-Exotic 3 3 3 Bobaya 3 3 3 Bobia 3 3 3 Buenaventura 3 3 3 Cabassou 3 3 3 Chikungunya 3 3 3 Chim 3 3 3 Cocal 3 3 3 Congo 4 4 4 Dhori 3 3 3 Dugbe 3 3 3 Eastern Equine Encephalitis (v) 2 3 3 Ebola 4 4 4 Everglades (v) 3 3 3 Ganjam (x) 3 3 3 Garba 3 3 3 Germiston 3 3 3 Getah 3 3 3 Gordil 3 3 3 Guaratuba 3 3 3 Hanzalova 4 4 4 Hypr 4 4 4

Ibaraki 3 3 3 Inhangapi 3 3 3 Inini 3 3 3 Israel Turkey Men. 3 3 3 Issyk-Kui 3 3 3 Itaituba 3 3 3 Japanese Encephalitis 3 3 3 Junin 4 4 4 Kairi (x) 3 3 3 Khasan 3 3 3 Koutango 3 3 3 Kumlinge 4 4 4 Kyasanur Forest Disease 4 4 4 Kyzylagach 3 3 3 Lassa 4 4 4 Louping ill (x) 3 3 3 Machupo 4 4 4 Marburg 4 4 4 Mayaro 3 3 3 Middelburg 3 3 3 Mosqueiro 3 3 3 Mucambo (v) 3 3 3 Murray Valley Encephalitis 3 3 3 Nairobi Sheep Disease (x) 3 3 3 Nariva 3 3 3 Ndumu 3 3 3 Negishi 3 3 3 New Minto 3 3 3 Nodamura 3 3 3 Northway 3 3 3 Omsk Hemorrhagic Fever 4 4 4 Oropouche 3 3 3 Orungo 3 3 3 Ouango 3 3 3 Oubangui 3 3 3 Paramushir 3 3 3

Piry 3 3 3 Ponteves 3 3 3 Powassan 3 3 3 Razdan 3 3 3 Rift Valley Fever (vx) 3 4 4 Rochambeau 3 3 3 Rocio 3 3 3 Russian Spring-Summer Enc. 4 4 4 Sagiyama 3 3 3 Sakpa 3 3 3 Salanga 3 3 3 Santa Rosa 3 3 3 Saumarez Reef 3 3 3 Semilki Forest 3 3 3 Seplik 3 3 3 Serra do Navio 3 3 3 Slovakia 3 3 3 Spondweni 3 3 3 St. Louis Encephalitis 3 3 3 Tamdy 3 3 3 Telok Forest 3 3 3 Tlacotalpan 3 3 3 Tonate 3 3 3 Venezuelan Equine Enc. (v) 3 3 3 (*) VEE (TC83) (v) 2 3 3 VS-Alagoas 3 3 3 VS-indiana 2 3 3 VS-New Jersey 2 3 3 Wesselsbron (x) 3 3 3 Western Equine Enc. (v) 2 3 3 West Nile 3 3 3 (*) Yellow Fever (17D) (v) 2 3 3 Zinga 3 3 3

ANSI,ISO,DIN,EN IntenationalISO Standard Office Deutsche Industrie NormaDIN American National Standard InstituteANSI

Laboratory Aquired Infections. C.H. Collins (ed.), Butterworth & Co. London, 1983. Laboratory safety. Theory and Practice. A.A. Fuscaldo. B.J. Erich & B,J, Hindman (eds.), Academic Press. New York, 1980. NIH Laboratory Safety Monograph. A Supplement to the NIH Guidelines for Recombinant DNA Research. U.S. Dept. of H.E.W. Pub. Health Service/ N.I.H. July, 1978. NIH Biohazards Safety Guide. U.S. Dept. of H.E.W. Pub. Health Service. 1974. Handbook of Laboratory Safety. N.V. Steere. The Chemical Rubber Co, Ohio, 1967. Biohazards in Biological Research. A. Hellman, M.N. Oxman & L.R. Pollack (eds.), Cold Spring Harbor Laboratory, 1973. Biosafety in Microbiological and Biomedical Laboratories. U.S.D.H.S. Public Health Service. Center for Disease Control & National Institute of Health, 2007. Laboratory Safety Manual. World Health Organization. Geneva, 2005. Laboratory Safety: Principles and Practices. D.O. Fleming (ed.), American Society of Microbiology, Washington, 1995. Israeli, E. Biosafety: in Biotechnological Processes. A Mizrahi (ed.), Advances in Biotechnological Processes.Vol. 6, Alan R. Liss, Inc. New York. 1986