PHARMACEUTICAL MICROBIOLOGY AND PARASITOLOGY Virology Ms. Pauline Lyzell Francisco, RPh, MSHSA I. INTRODUCTION TO VIRUSES o o o o o o o o o GENERAL CHARACTERISTICS Obligatory intracellular parasites Contain DNA or RNA No ribosomes No ATP-generating mechanism Contain a protein coat Some viruses are enclosed by an envelope Some viruses have spikes Most viruses infect only specific types of cells in one host Host range is determined by specific host attachment sites and cellular factors 10/28/2022 John Jeamel Igpuara, SPh MORPHOLOGY OF VIRUSES a. Polyhedral virus; “many sides” Icosahedron; 20 triangular faces, 12 corners e.g. Mastadenovirus, Poliovirus, Adenovirus VIRUS SIZES Covid-19 (SARS-CoV-2) – 60-140 nanometers Rhinovirus – common cause of colds/flu b. Enveloped icosahedral virus e.g. Herpesvirus, Human herpesvirus (HHV) VIRION STRUCTURE i. Nucleic Acid (DNA only / RNA only) NOT BOTH!! ii. Capsid; made of capsomeres (protein) iii. Envelope (lipids, proteins, carbohydrates) iv. Spikes (glycoprotein projection) Non-enveloped virus = naked virus o More resistant to changes 1 PHARMACEUTICAL MICROBIOLOGY AND PARASITOLOGY Virology Ms. Pauline Lyzell Francisco, RPh, MSHSA c. Enveloped helical virus e.g. Influenzavirus 10/28/2022 John Jeamel Igpuara, SPh TAXONOMY OF VIRUSES Family names ends in –viridae Genus names ends in –virus Viral species: o a group of viruses sharing the same genetic information and ecological niche (host) o common names are used for species o subspecies are designated by a number Example: Family Herpesviridae Retroviridae Genus Herpesvirus Lentivirus Human Human herpesvirus Species immunodeficiency virus HHV-1, HHV-2, HHV-3 HIV-1, HIV-2 d. Helical virus; like long rods, either rigid or flexible e.g. Ebola virus e. Complex viruses; polyhedral + helical e.g Bacteriophage, Orthopoxvirus II. VIRAL MULTIPLICATION a. Lytic Cycle - Bacteriophage causes lysis and death of host cell - Bacterial cells infected are called lytic cells. STEPS: 1. Attachment: phage attaches by tail fibers to the host cell 2. Penetration: phage lysozyme opens the cell wall; tail sheath contracts to force tail core and DNA into the cell 3. Biosynthesis: production of phage DNA and proteins 4. Maturation: assembly of phage particles 5. Release: phage lysozyme breaks the cell wall Viral one-step growth curve: 2 PHARMACEUTICAL MICROBIOLOGY AND PARASITOLOGY Virology Ms. Pauline Lyzell Francisco, RPh, MSHSA THE LYTIC CYCLE 10/28/2022 John Jeamel Igpuara, SPh THE MOVEMENT OF VIRUSES (ENTRY/EXIT) a. Endocytosis; “engulfing” - Togavirus b. Fusion; “merging with host” - Herpesvirus b. Lysogenic Cycle - These bacteriophages establish a stable, long-term relationship with their host called lysogeny. - Bacterial cells infected are called lysogenic cells. c. Budding; “formation of buds” - Lentivirus LIFE CYCLE OF VIRUS OTHER THAN PHAGES 3 PHARMACEUTICAL MICROBIOLOGY AND PARASITOLOGY Virology Ms. Pauline Lyzell Francisco, RPh, MSHSA III. LATENT AND PERSISTENT VIRAL INFECTIONS a. Latent viral infection o Virus remains in the asymptomatic host cell for long periods, sudden manifestation e.g. Cold sores, shingles (kulebra) caused by varicellazoster virus (also causes chicken pox) 10/28/2022 John Jeamel Igpuara, SPh 3. Papovaviridae - DSDNA, non-enveloped virus i. Papillomavirus – Human wart virus ii. Polyomavirus – causes tumors; some cancer b. Persistent viral infection o Disease process occurs over a long period; generally is fatal e.g. Subacute sclerosing panencephalitis (measles virus) IV. VIRUSES AND INFECTIOUS DISEASE DNA CONTAINING VIRUSES Non-enveloped 1. Parvoviridae - SSDNA, non-enveloped virus i. Fifth disease (Parvovirus B-19) more in kids Enveloped 4. Poxviridae - DSDNA, enveloped virus - Causes puss-filled skin lesions i. Orthopoxvirus (vaccinia and smallpox viruses) ii. Molluscipoxvirus iii. Smallpox iv. Molluscum contagiosum v. Cowpox ii. Anemia in immunocompromised patients 2. Adenoviridae - DSDNA, non-enveloped virus i. Respiratory infections in humans ii. Tumors in animals iii. Mastadenovirus Figure 1 Smallpox 4 PHARMACEUTICAL MICROBIOLOGY AND PARASITOLOGY Virology Ms. Pauline Lyzell Francisco, RPh, MSHSA 5. Herpesviridae - DSDNA, enveloped virus - Some can remain latent in host cells i. Simplexvirus (HHV-1, HHV-2); causes cold sores 1. Encephalitis (HHV-1); 2. STD/genital herpes/carcinoma (HHV-2) 10/28/2022 John Jeamel Igpuara, SPh 2. Caliciviridae - SSRNA, + strand, non-enveloped i. Hepatitis E virus o obtained via consumption of eating or drinking contaminated food or water, handmouth, close contact ii. Norovirus; causes gastroenteritis 3. Togaviridae - SSRNA, + strand, enveloped i. Alphavirus o Transmitted by arthropods (arbovirus); o EEE (Eastern Equine Encephalitis) and; o WEE (Western Equine Encephalitis) ii. iii. iv. v. vi. vii. Varicellovirus (HHV-3); causes chickenpox (VZV) Lymphocryptovirus (HHV-4) Cytomegalovirus (HHV-5); infants Roseolovirus (HHV-6, HHV-7) Rhadinovirus (HHV-8); causes Kaposi’s sarcoma Epstein-Barr virus (EBV); causes mononucleosis o ii. Rubivirus (rubella virus); causes German measles 6. Hepadnaviridae - DSDNA, enveloped virus - Uses reverse transcriptase i. Hepatitis B virus (HBV) -common form, obtained via hypodermic needles, blood transfusion, sex, contaminated needles/syringes RNA CONTAINING VIRUSES Positive (+) sense strand 1. Picornaviridae - SSRNA, + strand, non-enveloped i. Enterovirus (Poliovirus and coxsackievirus) ii. Rhinovirus (major cause of common colds) iii. Hepatitis A virus (jaundice) - obtained via fecal-oral route – G.I. (street foods) 4. Flaviviridae - SSRNA, + strand, enveloped i. Arboviruses - can replicate in arthropods o “Arthropod-borne virus” = Arbovirus o Yellow fever; monkey o Dengue a.k.a. breakbone fever; Aedes aegypti o SLE (St. Louis Encephalitis); wild birds/mosquito o West Nile viruses ii. Hepatitis C virus 5. Coronaviridae - SSRNA, + strand, enveloped - Upper Respiratory Infection (URI/URTI) i. Coronavirus ii. SARS, MERS 5 PHARMACEUTICAL MICROBIOLOGY AND PARASITOLOGY Virology Ms. Pauline Lyzell Francisco, RPh, MSHSA Negative (-) antisense strand 6. Rhabdoviridae - SSRNA, - strand, one RNA strand - Cause numerous animal diseases i. Vesiculovirus ii. Lyssavirus (rabies virus); dogs 7. Filoviridae - SSRNA, - strand, one RNA strand - Enveloped helical viruses; elongated i. Filovirus ii. Ebola a.k.a. African Hemmorhagic Fever iii. Marburg 8. Paramyxoviridae - SSRNA, - strand, one RNA strand i. Paramyxovirus ii. Morbillivirus iii. Parainflueza iv. Mumps; Parotitis enlargement of parotid glands v. Newcastle disease (chickens) 10/28/2022 John Jeamel Igpuara, SPh 10. Orthomyxoviridae - SSRNA, - strand, multiple RNA strands - Envelope spikes can agglutinate RBCs i. Influenzavirus (Influenza viruses A and B) ii. Influenza C virus 11. Bunyaviridae - SSRNA, - strand, multiple RNA strands i. Bunyavirus (California Encephalitis virus) o 4 types of disease syndrome a. Fever b. Encephalitis c. Hemorrhagic fever d. Acute Respiratory Illness ii. Hantavirus 12. Arenaviridae - SSRNA, - strand, multiple RNA strands - Helical capsids contain RNA-containing granules i. Lymphocytic choriomeningitis ii. VEE (Venezuelan Equine Encephalitis) iii. Lassa fever OTHER RNA VIRUSES 13. Retroviridae - SSRNA, two RNA strands, produce DNA - Uses reverse transcriptase to produce DNA from viral genome i. Lentivirus (HIV); Kaposi’s sarcoma ii. Oncogenic viruses o Includes all RNA tumor viruses 14. Reoviridae - DSRNA, non-enveloped i. Reovirus (respiratory enteric orphan) ii. Rotavirus (mild respiratory infections and gastroenteritis) iii. Colorado tick fever 9. Deltaviridae - SSRNA, - strand, one RNA strand - Depends on coinfection with hepadnavirus i. Hepatitis D virus – can only occur when with HBV 6 PHARMACEUTICAL MICROBIOLOGY AND PARASITOLOGY Virology Ms. Pauline Lyzell Francisco, RPh, MSHSA 10/28/2022 John Jeamel Igpuara, SPh V. VIRUS AND CANCER MOLECULAR BIOLOGICAL RESEARCH Shows that mechanisms of diseases are similar even when the virus does not cause cancer PLANT VIRUSES AND VIROIDS CANCER Activated oncogenes transform normal cells into cancerous cells; indirectly causing cancer Viruses capable of inducing tumors in animals are called oncogenic viruses, or oncoviruses The genetic material of oncogenic viruses becomes integrated into the host cell’s DNA ONCOGENIC VIRUSES Oncogenic DNA viruses i. Adenoviridae ii. Papovaviridae iii. Poxviridae iv. Herpesviridae v. Hepadnaviridae Oncogenic RNA viruses i. Retroviridae - Viral RNA is transcribed to DNA which can integrate into host DNA ii. HTLV-1 iii. HTLV-2 More common oncogenic viruses: o Human Papillomavirus o Epstein-Barr virus o Herpes simplex virus 2 PRIONS Proteinacious infectious particle Inherited and transmissible by ingestion, transplant, and surgical instruments i. Spongiform encephalitis: sheep scrapie ii. iii. iv. v. Creutzfeldt-Jakob disease Gerstmann-Straussler syndrome Fatal-familial insomnia Mad cow disease PrPC - Normal cellular prion protein On cell surface (HPV) (EBV) (HSV-2) VI. VIROIDS AND PRIONS PLANT VIRUSES AND VIROIDS Viroids infect: i. Potatoes; potato spindle tuber disease PrPSc - Scrapie prion protein Accumulates in brain cells, forming plaques ii. Chrysanthemum; stunting their growth iii. Cucumber; cucumber pale fruit disease 7