Microbiology: Viral Pathogens PDF

1 Microbiology: The Bad Bugs Part IIIb: The Pathogenic Viruses BIOL2700 Version 04 Microbiology Pathogenic Viruses: Selected Types 2 Herpes Virus family HHV 1 & 2; VZV; EBV, and CMV Hepatitis viruses Hep A, B, and C. Picornaviruses and common cold viruses Human Papilloma Virus (HPV) Measles Influenz...

1 Microbiology: The Bad Bugs Part IIIb: The Pathogenic Viruses BIOL2700 Version 04 Microbiology Pathogenic Viruses: Selected Types 2 Herpes Virus family HHV 1 & 2; VZV; EBV, and CMV Hepatitis viruses Hep A, B, and C. Picornaviruses and common cold viruses Human Papilloma Virus (HPV) Measles Influenza HIV/AIDS, Zika, Ebola, Sin Nombre, SARS, JC, and D68 will get an update lecture during Unit 5 3 Microbiology DNA Viruses DNA Viruses Single Stranded Nonenveloped Examples: Parvovirus Double Stranded Enveloped Nonenveloped Examples: Examples: Smallpox Adenovirus All Herpes Viruses HPV Hepatitis B 4 Microbiology RNA Viruses RNA Viruses Single Stranded Enveloped Examples: Coronavirus Ebolavirus Hepatitis C HIV Influenza A/B Nonenveloped Examples: Enterovirus Rhinovirus Hepatitis A Double Stranded Nonenveloped Examples: Rotavirus Microbiology Pathogenic Viruses Important Considerations: Name of virus DNA or RNA? Ss or ds? Disease it causes Characteristics of disease, symptoms. Viral virulence factors Epidemiology: reservoirs, vectors Immunizations 5 Microbiology Pathogenic Viruses: Brief Review Non-cellular Microbes Consists of nucleic acid and capsid (protein) Some types possess envelope, spikes, accessory proteins Obligate intracellular parasites Nucleic acid enters host cell, directs operations New copies of viral nucleic acid, proteins made Virus depends on host cell biochemical machinery Following assembly, new virions escape to infect new hosts 6 Microbiology Pathogenic Viruses: Viral Attack Virus has ways of attacking Specific binding to host cell receptor Receptors involved in normal cell functions Virus may regulate cell division for its own replication Insertion of viral DNA into chromosome allows virus to hide from immune system Causes adjacent cells to fuse, allows cell to cell spread without leaving cell. Host Defenses: Previously discussed ways of defending Cell mediated immunity (T cells): infected cells killed. Antibodies intercept virions between cells, in fluids Interferon produces anti-viral state, prevents replication 7 Microbiology Pathogenic Viruses: Herpes Virus Family Human herpes viruses (HHV) now numbered But common names easier to use. As a family: ability to become latent; predilection for either nervous tissue or lymphocytes; ability to cause cancer. Of the more than 100 known herpes viruses, 9 routinely infect only humans. Herpes roster: Herpes simplex (1-2), Varicella zoster (3), Epstein Barr (4), Cytomegalovirus (5), Roseoloviruses (6A, 6B, 7), Kaposi's sarcoma-associated herpesvirus (8). 8 Microbiology Pathogenic Viruses: Herpes Simplex Viruses HHV1 (above the waist) Typically oral, cold sores; flu-like symptoms, etc. HHV2 (genital), STI and neonatal Painful, contagious sores on genitals, overlap w/ HHV1. Latency Viruses enter nearby nerve cells, remain until activated by stress of some sort, cause disease, then return. Spread and treatment: Person to person by direct contact; spread within host by forming syncytia, escape immune system. Virus may be secreted in saliva for up to 7 weeks after recovery and from genital lesions for 7-12 days Acyclovir helps; no cure, lifetime infection. 9 (HHV aka HSV) 10 Microbiology Pathogenic Viruses: Herpes family: Varicella Zoster Varicella: chicken pox; Zoster shingles (HHV 3): Chickenpox (not a pox virus), respiratory, disease becomes systemic with fever, malaise, skin lesions. Very contagious; usually mild, esp. in children Virus can become latent in nerves (DRG of spinal nerves) like Herpes simplex Recurrence: shingles; rash, pain, covers dermatomal pattern Acyclovir can lessen symptoms Beware of salicylates + viruses (and fevers!): Reyes syndrome Vaccination: available for both Varicella & Zoster Shingles Note how rash does not cross the midline. Shingles occurs most frequently on the trunk, but a Google search shows pictures of face, legs, etc. as well. Microbiology Pathogenic Viruses: Herpes family: EBV Epstein-Barr Virus (HHV 4) Cause of infectious mononucleosis Infects B cells and salivary glands Spread by respiratory droplets, kissing Sore throat, swollen glands and spleen Long lasting fatigue Lympho-civil war: cytotoxic T cells attack infected, altered B cells. Same virus causes B cell cancer (Burkitt’s lymphoma) in Africa The occurrence of cancer also has some relationship to malaria exposure 11 12 Microbiology Pathogenic Viruses: Herpes family: Cytomegalovirus CMV (HHV5): Infection results in enlarged cells (hence, “Cytomegalo-”) Widespread asymptomatic infections, latency Virus shed in body fluids: sex, birth, transplants Problem for unborn, immunosuppressed, transplant patients; major cause of viralinduced birth defects. Normal Retina CMV Retinitis Rubella, a togavirus, was once the major viral cause of birth defects. Microbiology Pathogenic Viruses: Herpes family: Roseoloviruses Roseoloviruses (6A, 6B, 7): Cause of Sixth disease (roseola infantum, exanthem subitum) Classic presentation of a fever of rapid onset followed by a rash, both lasting 3-5 days. Complications may include febrile seizures, with serious complications being rare. Spread is usually through the saliva of those who are otherwise healthy. However, it may also spread transplacentaly during pregnancy. 13 Microbiology Pathogenic Viruses: Herpes family: Kaposi's sarcoma-associated herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV or HHV-8). Causes Kaposi's sarcoma, a cancer commonly occurring in AIDS patients. The sarcoma is a cancer that develops from the cells that line lymph or blood vessels. KSHV is transmitted mainly through saliva, but also transmissible via organ transplantation 14 Microbiology Pathogenic Viruses: What is Hepatitis? Hepatitis is inflammation of the liver Liver especially important in metabolism Breakdown of drugs, toxins, waste products Damage results in accumulation of bilirubin Bilirubin is a stage in hemoglobin breakdown Results in yellow color: jaundice Hepatitis can be caused by several different viruses Hepatitis A, B, and C viruses all cause liver damage, but are unrelated viruses. 15 Microbiology Pathogenic Viruses: Hepatitis B A DNA virus: “Hepadnavirus” Hepatitis B released from live cells, so accumulates in high numbers in body fluids. Blood of infected person is rather infectious Cuts, piercing, sex, childbirth, etc. Large amounts of empty capsids ties up antibodies. After exposure, long incubation, long disease 10% have chronic infections The younger the host, the likelier chronic infection Chronic infection correlated with liver destruction Liver tissue replaced by scar tissue; liver failure Long term exposure to virus increases risk of liver cancer Insertion of HBV DNA into chromosome may activate oncogenes Vaccination: routine for children starting ~1991 Recombinant vaccine. 16 Microbiology Pathogenic Viruses: Hepatitis A A small RNA virus, “Picornavirus” Transmitted by fecal-oral route Incubation for 1 month, followed by fever, nausea, anorexia, jaundice T cells attack infected liver cells No chronic infections, patients recover. Note comparisons to Hepatitis B: RNA vs DNA Shorter disease, few long term problems Mode of spread completely different 17 Microbiology Pathogenic Viruses: Hepatitis C Another RNA virus, different group: “Flavivirus” Causes chronic infections >80% Often mild with few symptoms until damage Long period between infection and damage Long term infections increase risk of cancer. Transmission like Hep B: blood, sex, transplants Curable with sofosbuvir/ledipasvir: blocks viral proteins 18 Microbiology Pathogenic Viruses: Human Papilloma Virus (HPV) Many Serotypes: 1,2-plantar and common warts 6,11-condylomata and laryngeal warts 16,18, 31 and othersanogenital malignancies Picture of HPV-1 capsids isolated from foot warts 19 Microbiology Pathogenic Viruses: HPV Genital Warts Usually caused by HPV 6 or 11 Prevalence had increased 2-10x during 30 year period prior to vaccine; Now down ~56% Most often found on penile shaft and anus in men, vulva in women Spontaneous regression seen in 20% of cases Treatments are ablative in nature Respiratory Also caused by 6 and 11 Pre-school children-bronchiolitis Adults-orogenital contact Potentially increasing in HIV+ individuals Anogenital Malignancy Caused by high risk HPVs-16, 18, 31 and others Occurs mainly in older women-average age 54 years Over 35% mortality Associated with increased number of sexual partners Prophylactic and Therapeutic Vaccines are available 20 Microbiology Pathogenic Viruses: Picornaviruses 21 Small RNA viruses (“pico” = very small) About 25 nm, near the size of a ribosome Many kinds of troublemakers, but two basic themes… Enteric viruses includes the previously mentioned Hepatitis A, as well as polio Only some cases of polio result in paralysis Includes Enterovirus A-D Cause of many cases of “stomach flu” D68 can cause a “polio-like” syndrome Rhinoviruses: major cause of common cold Rhino refers to the nose http://poliodematha.weebly.com/polio-from-start-to-finish.html 22 Microbiology Pathogenic Viruses: Picornaviruses They Make A Lot of Trouble… Heart: Coxackie & Echovirus Myocarditis Brain & Meninges: Coxackie, Echovirus, Enterovirus Meningitis, Encephalitis Skin: Coxackie Hand, Foot & Mouth Pharynx: Coxackie Herpangina GI Tract: Enterovirus Diarrheal Syndromes, Hepatitis (A) Picornaviruses Spinal Cord (LMN): Poliovirus Paralysis Nasal Passage: Rhinovirus (>100 serotypes) Common Cold Eye: Coxackie, Enterovirus Conjunctivitis Microbiology Pathogenic Viruses: Rhinoviruses & The Common Cold Rhinoviruses have many serotypes Variants, caused by easy mutation of RNA Immune system can’t recognize all differences, but some protection with age. Multiplies in narrow temperature range, nose/sinus cooler than body temperature Other cold viruses (not Picornaviruses) Coronavirus (As you know, some versions can cause SARS. Full Report Coming in Unit 5!) Adenovirus (DNA virus), some serotypes cause GI infections 23 http://www.the-scientist.com/?articles.view/articleNo/34189/title/Catching-the-Cold/ Microbiology Measles 24 Morbillivirus: non-segmented., linear., ssRNA, helical capsid, enveloped First described in 7th century Measles transmission is primarily person to person via large respiratory droplets. Airborne transmission via aerosolized droplet has been documented in closed areas (e.g., office examination room) for up to 2 hours after a person with measles occupied the area. Measles is highly communicable, with >90% among susceptible persons. Measles may be transmitted from 4 days prior to 4 days after rash onset. Maximum communicability occurs from onset of symptoms through the first 3-4 days of rash. Measles is a human disease. There is no known animal reservoir, and an asymptomatic carrier state has not been documented. Virulence 1. Portal of entry: Maculopapular – Respiratory mucus membrane. describes a rash that contains both macules 2. Attachment: and papules. A macule – Hemagglutinin: like influenza uses is a flat discolored area 3. Evade the immune system: of the skin, and a – Immunosuppression: papule is a small The measles virus blocks TH proliferation response to IL-2. raised bump. A maculopapular rash is The virus also destroys memory B-cells! usually a large area Measles virus infection diminishes preexisting antibodies that offer protection that is red, and has from other pathogens. Mina. Et al. Science 01 Nov 2019:Vol. 366, Issue 6465 small, confluent 4. Destruction of tissue: bumps. The maculopapular rash is caused by immune T-cells targeted to the infected endothelial cells of the small blood vessels. 25 Microbiology Measles Signs & Symptoms: Fever Malaise Maculopapular rash on palms and soles sore throat Rhinorrhea Cough Conjunctivitis Koplik spots: Found in the mouth, these spots look like tiny grains of white sand, each surrounded by a red ring. Quick Summary Reservoir: Human Transmission: Respiratory/Airborne Temporal pattern: Peak in late winter–spring Communicability:4 days before to 4 days after rash onset. 900 800 Cases (thousands) Signs & Symptoms 700 600 500 400 300 200 100 0 1950 1960 1970 1980 1990 2000 Microbiology Measles SSPE: Subacute sclerosing panencephalitis Measles is especially hard on children (The recent outbreak in Samoa resulted in >80 deaths: https://www.who.int/docs/default- Pneumonia in 1 out of every 20 Encephalitis in1-2 out of every 1000 source/wpro---documents/dps/outbreaks-andemergencies/measles-2019/measles-pacific-who-unicefsitrep-20200103.pdf?sfvrsn=82f90381_2) It can kill during the initial illness or leave a child with permanent cognitive impairment or hearing loss. SSPE occurs when infection of the brain becomes clinically apparent years later, often after an otherwise mild and uncomplicated case. Insidious onset (may be as long as 6-8 years after the measles), early dementia, disturbed motor function, myoclonic jerks, seizures, focal retinitis with optic atrophy, cerebellar ataxia leading to stuporous rigid state progresses to death in 1 to 3 years MMR Vaccine Failure 26 2-5% of recipients do not respond to the first dose Caused by antibody, damaged vaccine, record errors Most persons with vaccine failure will respond to second dose Measles vaccine is a live, attenuated measles virus grown in chick embryo tissue culture. In the United States, it is given as part of the MMR vaccine. Vaccine is about 95% effective Cases continue to occur among those who do not develop or retain good immunity, or those who avoid vaccinations.. MMR Vaccine and Autism Measles vaccine connection first suggested by (since delicensed) British gastroenterologist Diagnosis of autism often made in second year of life Multiple studies have shown NO association Microbiology Pathogenic Viruses: Orthomyxovirus Influenza: a wide-spread and still very dangerous respiratory disease Types A,B,C Virus has a segmented genome 8 different RNA molecules Spikes: Hemagglutinin and Neuraminidase Major antigens recognized by immune system Antigenic drift and shift Drift: small mutations, making host susceptible Requires new vaccine each year HA and NA accumulate mutations immune response no longer protects fully sporadic outbreaks, limited epidemics Shift: major mixing of RNAs, whole new virus. “new” HA or NA proteins pre-existing antibodies do not protect may get pandemics 27 28 Microbiology Pathogenic Viruses: Orthomyxovirus HA - hemagglutinin NA - neuraminidase helical nucleocapsid (RNA plus NP-RNA binding protein) lipid bilayer membrane polymerase complex (required for virus transcription and replication) M1 protein type A, B, C : NP, M1 protein sub-types: HA or NA protein Microbiology Pathogenic Viruses: “Flu”? True influenza – influenza virus A or influenza virus B (influenza virus C infections are much milder) Febrile respiratory disease with systemic symptoms caused by a variety of other organisms often called “flu” Nature of Influenza Attack on respiratory tract Kills ciliated epithelial cells, allows bacterial infections. Release of interferon causes symptoms H antigen (hemagglutinin) for attachment The fact that it agglutinates RBCs is an artifact N antigen: neuraminidase Cuts off the sugar on the glycoprotein receptor Allows new virions to escape from cell without getting stuck 29 30 Microbiology Pathogenic Viruses: Influenza Changes in H and N (antigenic shift) – Mixing of viruses that infect birds, pigs, produce new strains able to jump to humans. – New antigenic type leaves population unprotected – Numerous epidemics throughout history Flu of 1918-1919 killed 20 million – Asia watched very carefully: bird flu? Flu vaccines made from deactivated viruses – Slow process (vaccine made in eggs), so every year correct strains are “guessed”. – Cell culture would be quicker but more $ Yes… Best guess’ of main Antigenic types –Currently type A - H1N1 type A - H3N2 type B Microbiology Pathogenic Viruses: Influenza Meds { Rimantadine: Type A only, needs to be given early31 Amantadine: Type A only, needs to be given early Zanamivir: Types A and B, needs to be given early Oseltamivir: Types A and A, needs to be given early Spread Via: Aerosol 100,000 TO 1,000,000 VIRIONS PER DROPLET 18-72 HR INCUBATION Body Response: Lots of Interferon!- Side Effects: Fever, myalgia, fatigue, malaise, cell-mediated immune response Antibody Induction! IgG and IgA IgG less efficient but lasts longer antibodies to both HA and NA important antibody to HA more important (neutralize virus) Major causes of influenza virus- associated death Bacterial pneumonia Cardiac failure 90% of deaths in those over 65 years of age Diagnosis: Isolation Nose or Throat Swab Tissue or Egg Culture Serology (Blood Analysis) Provisional: Clinical picture + Outbreak Complications: Secondary bacterial infection Strept pneumoniae Staph aureus Hemophilus influenzae Myositis (rare, > in children, > with type B) Cardiac complications Liver and CNS Reye syndrome Peripheral nervous system Guillian-Barré syndrome