Homeostasis

TPs Printed 10/28/2009 BIOL208 Unit 4 Chapters 06, 09, 24, 25 Page 1 of 19 Virology--Chapter 6, Chapter 9 (pp. 270-273), Chapters 24 & 25 Bacteria vs. Viruses Bacteria Procaryotic cells Both DNA and RNA Ribosomes Free-living or Parasites 1-2 micrometers in size Viruses Genome plus capsid Either DNA or RNA No ribosomes Obligate intracellular parasites 20-250 nanometers in size Virus Structure Genome: either DNA or RNA (not both) Capsid: consists of protein capsomeres  Capsid - protein shell surrounding nucleic acid cord  Capsomere - a number of identical protein subunits Nucleocapsid   Consists of capsid with genome (capsid + nucleic acid) Icosahedral, helical, or complex Naked virus - consists of only a nucleocapsid Genome - sum total of genetic information carried by an organism; genome of organisms is carried and expressed by its nucleic acids Envelope: when present, derived from host membrane and viral proteins    "Naked" viruses resist desiccation better Viral enzymes may or may not be present in free virus particles. Examples: Neuraminidase in influenza virus Reverse transcriptase in HIV TPs Printed 10/28/2009 BIOL208 Unit 4 Chapters 06, 09, 24, 25 Page 2 of 19 TPs Printed 10/28/2009 BIOL208 Unit 4 Chapters 06, 09, 24, 25 Page 3 of 19 Bacteriophage Replication Page 177, figure 6.18 Phages attach to specific host cells through adsorption Injection of nucleic acid Phage replicates proteins and nucleic acid using host "machinery" Assembly Release Lytic cycle versus Lysogeny Figure 6.17, page 176 Page 177, table 6.5 Lysogeny - results in spread of a virus without killing the host cell  Viral DNA is inserted into bacterial chromosome, remaining inactive for an extended period.  Viral DNA is replicated right along with the chromosome each time the bacterium divides, usually unnoticed. TPs Printed 10/28/2009 BIOL208 Unit 4 Chapters 06, 09, 24, 25 Page 4 of 19 Animal Virus Replication Prophage - integrated DNA Many viruses are very particular about who they can effect 1. Adsorption: (physical attachment between two particles) attachment to host receptor 2. Penetration   Fusion Viropexis (similar to pinocytosis) - cell drinking Host specificity (range) - certain animal viruses are specific about what organisms it affects.  Ex: rubella is specific to humans Tissue tropism - certain viruses tend to infect only certain types of tissues and cells.  Rabies affects neurological tissue  Hepatitis affects liver tissue. 3. Uncoating: host lysosomal enzymes facilitate removal of capsid 4. Early Protein Synthesis   Enzymes Replicative proteins 5. Nucleic Acid Replication 6. Late Protein Synthesis  Structural proteins Assembly and Release Herpes - latent infections HIV - RNA virus - infects primates; reverse transcriptase - makes DNA from RNA Rubella human is only host Hog Cholera - pig host Rabies - humans, dogs, cats, receptor is widely distributed Avian Flu TPs Printed 10/28/2009 BIOL208 Unit 4 Chapters 06, 09, 24, 25 Page 5 of 19 DNA Viruses (see chapter 9, pages 273275) Double-stranded DNA viruses Oncogenic HPV - can cause cancer Single-stranded DNA viruses Viral DNA enters nucleus where several genes are transcribed into mRNA mRNA moves into cytoplasm to be translated into viral proteins (enzymes) needed to replicate viral DNA (occurs around the nucleus) Late phase, other parts of viral genome are transcribed and translated into proteins required to form capsid and other structures. New viral genomes and capsids are assembled and mature viruses exit by budding or lysis. (Double stranded DNA can insert itself into host DNA latency) RNA Viruses Double-stranded RNA viruses Ex: Rotavirus Single-stranded RNA viruses (positive polarity: viral RNA = messenger RNA) - ready to go and be translated into proteins Rubella, Polio, Hepatitis A Single-stranded RNA viruses (negative polarity: viral RNA -does not = mRNA) - not ready; must be converted to positive sense Parvoviruses Retroviruses: reverse transcriptase copies RNA into DNA AIDS Transcription in reverse (RNA dependent, DNA polymerase); use RNA as a template to build DNA Need to understand mechanical aspects See picture on page 275 Enter the cell already in an RNA form Virus cycle - in cytoplasm Virus enters cytoplasm Replicate a negative strand as a master to produce more positive strands TPs Printed 10/28/2009 BIOL208 Unit 4 Chapters 06, 09, 24, 25 Page 6 of 19 Virus uncoats in cell; positive strand is translated into protein that is cleaved into functional units (one is RNA polymerase), so it can start viral replication Negative strand is synthesized using usual base-pairing Negative strand becomes master for several daughter strands produced. Further translation produces large numbers of structural proteins for final assembly and maturation of virus. TPs Printed 10/28/2009 BIOL208 Unit 4 Chapters 06, 09, 24, 25 Page 7 of 19 Virus Cultivation Viruses require live cells for replication (p. 178)     Live animals Embryonated eggs Cell culture (or tissue culture) Contact inhibition Detecting virus growth (p. 179)  Plaques - clear, well-defined patches on a cell sheet Vaccines "Live" attenuated virus vaccines Live - meaning viable if placed in an appropriate cell Live but very effective for a long period of time Need to be very careful around immune-comprised people     Attenuation of viruses (attenuate - less virulent) Mutant viruses "Herd immunity" - give vaccine to one individual and its affects spread by natural means to everyone else. Examples: o Sabin polio virus vaccine (OPV) Not everyone needs to be vaccinated Cost effective and easy to administer 3 or 4 people each year might come down with polio; changed methods o MMR (measles, mumps, and rubella) o Varicella (chickenpox) Flu mist - administered through respiratory tract If administered through natural way, could get a good immune response in respiratory tract Non-living vaccines May not last as long as an attenuated vaccine    Inactivated whole virus vaccines Subunit vaccines Examples: o Salk polio virus vaccine (IPV) No chance of getting disease; injection o Influenza virus vaccine o Hepatitis B virus vaccine Subunit vaccine TPs Printed 10/28/2009 BIOL208 Unit 4 Chapters 06, 09, 24, 25 Page 8 of 19 See Immune Schedule, CDC, 2007 attachment TPs Printed 10/28/2009 BIOL208 Unit 4 Chapters 06, 09, 24, 25 Page 9 of 19 Antiviral Chemotherapy Drugs for virus infections Interferon  Naturally occurring human cell product Amantadine (5ymmetrel) for Influenza A Neuraminidase inhibitors: Relenza (zanamivir), Tamiflu (oseltamivir) for Influenza A and B If administered early, can help Acyclovir (Zovirax): for Herpes viruses infections (drug is activated to toxicity by viral-encoded thymidine kinase) Thymidine kinase - only found in virus-infected cells Azidothymidine (AZT or Retrovir): for HIV infection (AZT is an inhibitor of reverse transcriptase) Idoxuridine, Ara-A, Ara-C (base analogs) for serious viral infections Chapter 6 Questions, page 185: 2, 4, 5, 7, 9, 11, 12, 13, 14, 15 TPs Printed 10/28/2009 BIOL208 Unit 4 Chapters 06, 09, 24, 25 Page 10 of 19 Chapter 24 DNA Viruses Papovaviruses Start p. 746 Double-stranded DNA Non-enveloped (naked), icosahedral Polyoma viruses   BK Virus: oncogenic in vitro JC Virus: PML (Progressive Multifocal Leucoencephalopathy) Oncogenic in vitro - In vitro - in glass - in lab setting Causes cancer in the lab Papilloma Viruses  Human wart viruses o Common warts o Plantar warts o Genital warts (including condyloma acuminata) Genital warts linked to cancer (oncogenic) Treatment (when necessary): drugs, cryosurgery, or cauterization Poxviruses Start page 732 Double-stranded DNA Complex symmetry; enveloped Varieties:        Variola (smallpox) Vaccinia (cowpox, attenuated vaccine strains) Molluscum contagiosum (STD) Smallpox Infection: aerosol droplets or skin crusts Rash (macules-->papules-->vesicles--> pustules-->pocks) Variola major vs. Variola minor Progression of lesions (similar for chicken pox) TPs Printed 10/28/2009 BIOL208 Unit 4 Chapters 06, 09, 24, 25 Page 11 of 19 Parvovirus Single-stranded DNA Non-enveloped, icosahedral B19 Virus: Fifth's Disease: erythema infectiosum  Human risk - fairly common     "Slapped cheek" appearance Congenital transmission? Anemia Self-limiting Herpesviruses Start page 734 Double-stranded DNA Enveloped, icosahedral Many are capable of latency (Varicella-Zoster, HSV-1, HSV-2 - there may be more) Latency - term for animal viruses Some are known teratogens (CMV, Varicella-Zoster) Likely to cause developmental defects in babies Cytomegalovirus (CMV) important in: (Normal healthy adults don’t seem to have much problem)   Transplant recipients (via transplanted tissue or due to immunosuppression) Fetal infections (second trimester) o ToRCH Screen (Toxoplasma, Rubella, CMV, HSV) - Toxoplasma - a concern for AIDS patients; watch undercooked meat; protozoan parasite found in cat litter - pregnant women should stay away Varicella (Chickenpox)         Asynchronous lesions begin on trunk and face (macule, papule, vesicle, pustule, pock) Teratogenic (first trimester) Attenuated vaccine now in use Zoster (Herpes zoster or shingles) Often confined to one "dermatome" Epstein Barr Virus (EBV) Oncogenic Infectious mononucleosis Burkitt's lymphoma (Africa) Nasopharyngeal carcinoma (China) TPs Printed 10/28/2009 BIOL208 Unit 4 Chapters 06, 09, 24, 25 Page 12 of 19 Tends to reside in trigeminal nerves Herpes Simplex Virus 1 (HSV-1)  Cold sores  "Herpes labialis"  Also: conjunctivitis, gingivostomatitis, encephalitis Herpes Simplex Virus 2 (HSV-2)  "Herpes genitalis"  Also: neonatal, conjunctivitis, encephalitis Herpes Simplex - young baby exposed but did not have immunities?? Don’t rub your eyes. Other Herpesviruses:  Roseola (HHV-6)  HHV-7 (similar to HHV-6)  HHV-8 (Kaposi sarcoma-associated herpesvirus)  Monkey B Virus--may be fatal in humans Adenovirus Read about these. Double-stranded DNA Non-enveloped, icosahedral Pathogenesis: many varieties  Respiratory (pharyngitis: sore throat)  Pneumonia (lower respiratory infection)  Keratoconjunctivitis  Oncogenic (cancer) in laboratory animals, but not in humans Hepatitis B Virus (Hepadnavirus) Hepatitis B Virus: enveloped DNA virus  Unusual genome containing both double & single stranded DNA  Multiplies exclusively in the liver, which continuously seeds blood with viruses (107 virions/mL blood) Hepatitis B virus causes hepatitis & can be a factor in liver cancer Transmission:  Blood and body fluids sexually transmitted  High incidence among homosexuals & drug addicts Can become a chronic infection Increases risk of liver cancer Treatment/prevention:  Chronic infection controlled with interferon  HB immune globulin protects exposed people  HBV vaccine - recombinant surface antigen made by yeast; given in 3 doses over 18 months Table 24.3 - Review Chapter 24 Questions (pages 751-752): 2, 3, 4, 7, 8, 9, 10, 11, 12, 13, 16, 18, 19, 20 TPs Printed 10/28/2009 BIOL208 Unit 4 Chapters 06, 09, 24, 25 Page 13 of 19 Chapter 25 RNA Viruses Positive polarity - equivalent to mRNA Picornaviruses Pico - means small Single-stranded RNA (+ polarity) Non-enveloped, icosahedral Group I: Enteroviruses - intestines (fecal-oral route) Group II: Rhinoviruses - nose - respiratory Cold viruses, fomites, and aerosol secretions, fairly hardy outside of body TPs Printed 10/28/2009 BIOL208 Unit 4 Chapters 06, 09, 24, 25 Page 14 of 19 Group I Picorna - Enteroviruses Enteroviruses are classified because of mode of transmission Poliovirus     Primary invader of pharynx or intestine Secondary invader of blood, lymph, CNS Aseptic meningitis (1-2% of infections) Vaccines: o o Salk IPV (dead virus and usually used) Sabin OPV (given more many years ago, but some people got polio, especially immune compromised) Echovirus: aseptic meningitis, rash, diarrhea Coxsackievirus: herpangina, meningitis, myocarditis, "hand-foot-mouth" disease  Herpangina - mouth, lesions, pain  Meningitis - ascptic  Hang- foot-mouth disease - common childhood disease (not to be confused with the animal disease, hoof and mouth disease) Hepatitis A virus Improper handwashing in restaurants and daycares.    Causes short-term hepatitis Fecal-oral transmission Treatment/prevention o Inactivated viral vaccine attenuated viral vaccine o Pooled immune serum globulin Group 2 Picorna - Rhinoviruses Spread more commonly during the winter season Upper respiratory tract infections Perhaps 200 or more serotypes Replicate in respiratory epithelium no viremia or fever Transmission: fomites, aerosols, self-inoculation Do not stimulate a good immune response because they do not get into the blood TPs Printed 10/28/2009 BIOL208 Unit 4 Chapters 06, 09, 24, 25 Page 15 of 19 Togaviruses Single-stranded RNA (+) Enveloped, icosahedral Single-stranded, non-segmented Arboviruses (arthropod-borne): many, but not all, arthropod-borne viruses belong to the Togavirus family. Examples:    Eastern and Western Equine Encephalitis, St. Louis Encephalitis Yellow Fever (hemorrhagic) - used to be endemic in the southeastern United States - jaundice Dengue (arthralgic, "bone-break fever") - costal areas of the Caribbean; need to get rid of standing water o Arthropod born or arbovirus Non-arbo Togavirus  Rubella virus (German measles) - relatively rare anymore o Congenital Rubella Syndrome - common in 1960’s o Infection during first trimester most serious o Vaccination (MMR vaccine) Rubeola - regular measles Other Single-stranded (+) RNA Viruses Coronavirus     Single-stranded, non-segmented Colds, pneumonia, myocarditis Gastroenteritis SARS: Severe Acute Respiratory Syndrome (southeast Asia) Calicivirus Non-enveloped Single-stranded, non-segmented  Norwalk agent (Norovirus): gastroenteritis Reovirus - Rotavirus Segmented, double-stranded RNA virus Acute gastroenteritis in young children TPs Printed 10/28/2009 BIOL208 Unit 4 Chapters 06, 09, 24, 25 Page 16 of 19 Rhabdoviruses Single-stranded RNA (-) polarity Enveloped, non-segmented Bullet-shaped, helical morphology Rabies     Infects wide variety of mammals Humans infected through bites, fluids, transplants (rarely) Incubation up to 30 days Symptoms: neurological, throat spasms, convulsions Diagnosis: immunofluorescence, microscopic identification of Negri bodies Vaccination:   Preexposure: Human Diploid Cell Vaccine (HDCV) Postexposure: HDCV plus Human Rabies Immune Globulin (HRIG) plus Tetanus toxoid vaccine Paramyxoviruses Single-stranded RNA (-) viruses including: Mumps (epidemic parotitis) Parainfluenzae ("croup" or laryngo-tracheobronchitis) Measles (Morbillivirus, Rubeola)  Little spots on oral mucosa first   Koplik's spots, descending macular rash Complication: SSPE (subacute sclerosing panencephalitis) Respiratory syncytial virus (RSV or pneumovirus): epidemic viral pneumonia TPs Printed 10/28/2009 BIOL208 Unit 4 Chapters 06, 09, 24, 25 Page 17 of 19 Orthomyxoviruses (Influenza) Single-stranded RNA (-) polarity (With negative polarity, has to make duplicate strand of positive RNA before it can start making viral proteins Segmented genome (this allows mixing of genes) Influenza RNA varieties: A, B, and C     A and B responsible for human epidemics C causes minor respiratory symptoms Strains of A infect birds, pigs, horses - concerned here with antigenic shift Protein spikes common in human strains of influenza A Hemagglutinin (H) 0,1,2 or 3 - attachment protein o Clumps RBCs o H is a surface marker Neuraminidase (N) 1 or 2 - allows for release of virus o Enzyme - crucial for virus to get out of cell o Tamaflu - keeps neurominidase from working effectively Current Strains o o o A/Panama/2007/99 H3N2 A/Fujian/41112002 (H3N2 drift variant) A/New Calendonia/20/99-like (H1N1) 15 H variations total, 9 N variations total Avian (Bird) flu transmitted to humans: HSN1, H7N7, H9N2    Other variants in animals: o o Southeast Asia H5N1 - no innate immunity if no exposure for a long time Symptoms in humans: chills, fever, fatigue and aches Predominantly a respiratory virus Sequelae: Reye's Syndrome and Guillain Barre Syndrome (self-limiting paralysis) Variation Antigenic drift: point mutations in viral genome account for minor variations - all viruses Antigenic shift: major changes due to recombination and genome rearrangement - viruses with segmented genomes Prevention and Treatment:    Trivalent vaccination strains include: o A/New Calendonia (H1N1), A/Moscow (H3N2), B/Hong Kong Forms of vaccine: Injection (dead) or aerosols (attenuated). Flu mist - keep pregnant women and immune comprised away from this Drugs: o Amantadine (Symmetrel) o Neuraminidase inhibitors (Tamiflu and Relenza) TPs Printed 10/28/2009 BIOL208 Unit 4 Chapters 06, 09, 24, 25 Page 18 of 19 Other Virus Families ”Exotic” Virus Families High mortality rates, transmission varies Examples:    Bunyaviruses: Hantavirus Filoviruses: Ebola virus, Marburg virus (90% mortality) Arenaviruses: Lassa Fever - Africa; California Encephalitis Virus Page 756, figure 25.3 Retroviruses Single-stranded RNA Reverse Transcriptase present in virus     synthesizes DNA from RNA template DNA integrates into host chromosome Human Immunodeficiency Viruses HIV-1, HIV-2 infect cells with the CD4 receptor (Helper T cells, endothelial and, glial cells and some others) Retroviruses: Stages of HIV Infection (patient becomes sero-positive as virus replicates) Latency: virus resides intracellularly Activation of immune cells with virus leads to virus production and death of helper T cells Depletion of T cells may result in "full-blown AIDS" or "Acquired Immunodeficiency Syndrome" Opportunistic infections, increased tumor susceptibility HIV Drug Strategies Reverse transcriptase (RT) inhibitors: AZT Protease inhibitors Integrase inhibitors HAART: Highly active anti-retroviral therapy: "cocktail" of 2 RT inhibitors, 1 protease inhibitor TPs Printed 10/28/2009 BIOL208 Unit 4 Chapters 06, 09, 24, 25 Page 19 of 19 Table 25.A AIDS - Defining Illnesses "Slow Virus Diseases" Possible Agents   Conventional Viruses Viroids o Viruslike agents of plants o Composed of only naked strands of RNA; no capsid or coating (1/10 the size of average virus) o Attacks tomatoes, potatoes, cucumbers, citrus trees, chrysanthemums Prions o Naked protein molecules  Representative Slow Virus Diseases      Mad Cow Disease (Bovine Spongioform Encephalopathy) Creutzfeldt-Jakob Disease (CJD) Kuru Progressive Multifocal Leucoencephalopathy (PML): JC Virus Subacute Sclerosing Panencephalitis (SSPE): associated with Rubeola Chapter 25, Questions, pages 788-789: 1, 2, 5, 6, 7, 8, 9, 10, 11, 16, 17, 18, 19, 20