What is a Virus? Components of a Virus. BIOL 142 Lecture 10 Viruses. acellular. obligate intracellular parasites:

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1 BIOL 142 Lecture 10 Viruses 51 slides 1 What is a Virus? acellular no cell nucleus no organelles no cytoplasm obligate intracellular parasites: can replicate inside a living host cell. replication uses the cellular machinery of the cell that is being parasitized to make all the needed components. replication usually kills the host cell and results in hundreds to thousands of new viral copies. Contain only one kind of nucleic acid: DNA or RNA. 2 Components of a Virus Nucleic Acid Core: having RNA or DNA. single-stranded or double-stranded. linear, circular or segmented. Capsid: the protein coat that surrounds the nucleic acid core. Envelope: only present in some viruses is a lipid bilayer membrane can have spikes on it. A complete virus particle, including its envelope, if it has one, is called a virion. 3

2 Characteristics of a Virus Can not carry out any metabolic pathway. Do not grow. Do not respond to the environment. Can not reproduce independently. Must recruit (hijack) a cell s metabolic pathways to increase their numbers (reproduce). No cytoplasmic membrane. No cytosol. No organelles. Have an extracellular state & intracellular state. 4 Characteristics of a Virus Extracellular State: also called a Viron. is just the protein coat (capsid) some viruses also have a phospholipid envelope. function is to surround the nucleic acid and to provide it some protection and a site of recognition for host cells. Intracellular State: capsid is removed. virus exists as a nucleic acid (DNA or RNA). 5 Components of a Virus 6

3 Components of a Virus Capsid: determines the shape of a virus. Icosahedral (polyhedral), Helical & Complex. protects it. encloses the nucleic acid. plays a key role in the attachment of some viruses to the host cell. composed of subunits called capsomeres. can be a single protein that makes each capsomere or many. the arrangement and the number of proteins in the capsomeres can be useful in identification and classification. 7 Components of a Virus Envelope: typical bilayer membrane outside the capsid. acquired from the cell it is parasitizing as it buds through one or several membranes. some viruses have no envelope are are called: naked non-enveloped the composition of the envelope is derived from: the viral nucleic acid instructions. the substances found in the parasitized cell s membranes. Spikes: glycoproteins that project from some envelopes that serve to attach virions to specific receptor sites on susceptible host cell surfaces. Can result in hemagglutination. 8 Components of a Virus Envelope: can help a virus evade detection from the host s immune system. can help with fusion to make infection of new cells easier or possible. the envelope is easily damaged as the virus has NO way to repair it. it has no organelles nor genetic instructions to assist in its repair. very sensitive to temperature changes, ph, lipid solvents, chemical disinfectants... all of which will easily destroy the envelope. 9

4 Poliovirus: it infects the peyer s patches of the small intestine. this explains the fecal-oral mode of transmission. sanitation improvements have lowered its prevalence and incidence among children. it infects the motor neurons. this explains the paralysis. the chances of getting the paralytic poliomyelitis increases with age. Symptoms: mild fever and meningitis that lasts about a week. Paralytic Poliomyelitis arises when the virus destroys motor neurons in the spinal cord causing asymmetric paralysis and painful muscle spasms (no sensation is lost, just movement) 10 Poliovirus: Vaccine: inactivated polio vaccine: developed by Jonas Salk formalin-killed virus injected into the skin oral polio vaccine: developed by Albert B. Sabin attenuated poliovirus (lost its ability to multiply in the CNS) taken orally, replicates and is shed in the feces easier to administer to many people better immune response (IgA and IgG antibodies formed) can spread to others resulting in immunity in those people. 1 in 2.6 million chance of contracting vaccine-associated paralytic poliomyelitis

5 Rhinovirus: causes the common cold hundreds of serotypes transmission by hand-to-hand spread of mucous membrane secretions the CORONA viridae causes a common cold that is virtually indistinguishable from the one caused by Rhinovirus, but only about 15% are CORONA viridae. 13 Norwalk Virus causes diarrhea mostly in children named for an outbreak in a Norwalk, Ohio Elementary School where 50% of the school kids had diarrhea and vomiting. commonly found after hurricanes, floods & other sudden drops in sanitation as a cause of acute gastroenteritis (upset stomach, nausea, vomiting). 14 Mosquito-borne Encephalitis: WEE (Western Equine Encephalitis) EEE (Eastern Equine Encephalitis) VEE (Venezuelan Equine Encephalitis) symptoms: severe headache meningitis encephalitis 15

6 Yellow Fever: transmitted by mosquitoes develop hepatitis & jaundice 50% die from kidney failure Vaccine available Insecticides first US Biological warfare agent used during the Civil War. Dr. Luke Blackburn went to Bermuda in 1864 to help with yellow fever epidemic. collected soiled clothes and linens and planned to send them to various cities in the U.S. in trunks. plot foiled because Dr. Blackburn did not pay his assistant, who reported him to the authorities. Interestingly, Lincoln was assassinated two days later. would not have worked anyway... need a mosquito as a vector. 16 Hantavirus: can cause hemorrhagic fever with renal failure. Rodent Vectors: Deer Mouse No known treatment. 17 Measles (Rubeola): has HA (Hemagglutinin) no NA (Neuraminidase) F-protein (Fusion protein) results in multi-nucleated giant cells. Prodrome Symptoms: high fever, hacking cough, conjunctivitis Koplik s Spots: small red based, blue-white spots centered in lesions inside mouth. Rash: From Head, then to Neck & Torso, then to Feet. As the rash spreads it Coalesces. It disappears in the same sequence it develops. Measles Vaccine is live attenuated. 18

7 Mumps: has HA (Hemagglutinin) has NA (Neuraminidase) F-protein Fusion Protein: results in multi-nucleated giant cells. Symptoms: Painful Parotid Gland swelling Painful Testicular Inflammation Meningitis Encephalitis Mumps Vaccine is live attenuated. 19 Rabies: bullet-shaped, enveloped, helical. can infect all warm-blooded animals & each can serve as reservoirs. transmitted in saliva during a bite / scratch. virus migrates slowly up nerve axons to the CNS, causing a fatal case of encephalitis. this is a very slow incubation period (weeks to year) brain cells in rabies develop a characteristic feature called negri bodies in the cytoplasm. once brain symptoms develop, death is in 1 to 2 weeks from acute encephalitis (seizures, confusion, madness). 20 Rabies: Classic Brainstem Encephalitis: painful contractions of the pharyngeal muscles. difficulty swallowing liquids and saliva. causes hydrophobia causes foaming at the mouth Death: secondary to respiratory center dysfunction. highest case fatality ratio of any infectious disease. only one confirmed recovery from an active case of rabies: year old girl bitten by a bat. 76 days to recover. Vaccination with human rabies IgG & rabies vaccine. observe captured animal for 10 days for symptoms. 21

8 Marburg and Ebola Viruses: FILO viridae April 1995 in Zaire major outbreak of Ebola transmission secondary to contact with infected body fluids. blood primarily. feces, urine, and sputum no airborne transmission known. Hemorrhagic Fever 2 week incubation rapid death from multi-system organ failure. bleeding and fluid loss from very leaky blood vessels. 22 HIV-1 & HIV-2: carries a unique enzyme with the virus called reverse transcriptase that converts the viral RNA to DNA. the transcribed viral DNA can insert itself into the host s DNA. it causes a cancer in the cells they infect by activating genes called proto-oncogenes. eventually the infected cells are destroyed. the main cell destroyed in HIV infections is an immune cell called the T-helper lymphocyte. The symptoms of AIDS are a direct result of the activation of proto-oncogenes and the destruction of the T-helper lymphocytes. 23 HIV: Transmission via infected body fluids blood, semen, breast milk, IV drugs (any break in the skin) Acute Viral Illness: feels like mono (fever, body aches, sore throat) for 1 month. high levels of HIV at this stage. Clinical Latency: average is 8 years no symptoms lymphadenopathy starts to appear as CD4 T-helper lymphocytes are destroyed. AIDS: lasts about 2 years. Death from multiple infections. CD4 T-helper lymphocyte count <

9 DNA Viruses HERPES viridae general characteristics: they can develop a latent state. about 25% of previously infected people have reactivation infections during stressed states. the more immunocompromised the patient, the more severe the reactivation infection will be. some (the members in the sub-family alpha) have cytopathic effects on cells, which become multinucleated giant syncytial cells with intranuclear inclusion bodies. the way we fight them is by using our cell-mediated immune response. 25 DNA Viruses Latency: during the primary infection the viruses migrate up the nerves to the sensory ganglia and reside there. the virus rests there until reactivation through some sort of stress event on the body : anxiety (of any kind) stress (of any kind) menstruation sunlight exposure weakened cell-mediated immune system conditions: AIDS. Any Chronic Illness. the virus then migrate out to the peripheral skin via the nerves to cause local destruction. 26 DNA Viruses Cytopathic Effect: the HERPES viridae that cause cell destruction are the alpha sub group viruses: Herpes Simplex Virus 1 Herpes Simplex Virus 2 Varicella-Zoster this cell destruction results in the separation of the epithelium and causes blisters (vesicles). microscopic study of skin biopsies or scrapings from blister bases all reveal multinucleated giant cells and intranuclear inclusion bodies. viral proteins are inserted into the host s plasma membranes, resulting in cell fusion to form multinucleated giant cells. Intranuclear inclusions are areas of viral assembly. 27

10 DNA Viruses Cell-Mediated Immune Response: patients who have a compromised cell-mediated immune system are more likely to suffer from severe HERPES viridae infections: disseminated Herpes Simplex Virus multi-dermatomal zoster severe Cytomegalovirus (CMV) rare and severe presentations of the infections. 28 Herpes Simplex Virus 1 & 2: by their 40s: over 90% of adults will have antibodies to HSV-1. over 20% of adults will have antibodies to HSV-2. Transmission occurs by direct inoculation of mucocutaneous surfaces: Oropharynx (mouth and upper throat) Cervix (sexually transmitted) Conjunctivae (inside of eyelids) Small cracks in skin (penis, fingers, lips, etc...) NOTE: viral shedding can occur in the absence of lesions!!! clinical manifestations depend on the site of inoculation, and the immune status of the host 29 Herpes Simplex Virus 1 & 2: Clinical Presentations: Gingivostomatitis: painful swollen gums and mucous membranes with multiple vesicles. fever and systemic symptoms can accompany the infection. disease resolves in about 2 weeks. vesicles can appear on the skin where viral entry has occurred. Genital Herpes: despite common lore, genital herpes may be caused by HSV-1 or HSV-2, and are clinically indistinguishable. Fever headache, vaginal and urethral discharge enlarged lymph nodes blisters appear later which turn into painful or painless ulcerations. 30

11 Herpes Simplex Virus 1 & 2: Clinical Presentations: Herpetic Keratitis: most common infectious cause of corneal blindness in the USA. Neonatal Herpes: HSV infection during pregnancy can result in transplacental viral transfer (this is VERTICAL transmission of the infection). the infection of the fetus can cause congenital defects or intrauterine death. the neonate can also acquire the illness during delivery if the mother is having an active genital infection. Normally, this is an indication for a cesarean delivery. 31 Herpes Simplex Virus 1 & 2: Clinical Presentations: Herpetic Whitlow: is an HSV infection of a finger (typically near the fingernail border). the finger becomes painful, bright red, hot and very swollen. before the common use of gloves in the hospital, this was a common health-care worker infection! 32 Herpes Simplex Virus 1 & 2: Clinical Presentations: Disseminated Herpes: in immune compromised patients (organ transplant recipients, cancer chemotherapy, malnutrition, burns, etc...) HSV may cause extensive mucocutaneous infections, or disseminated infections to the Liver, Lung, and Gastrointestinal Tract. easily can lead to death. 33

12 Herpes Simplex Virus 1 & 2: Clinical Presentations: Encephalitis: HSV-1 is the most common cause of viral encephalitis in the USA. infection of the brain cells occurs causing cell death & brain swelling. sudden onset of fever focal neurological abnormalities one of the few treatable causes of viral encephalitis! 34 Herpes Simplex Virus 1 & 2: Diagnostics: Tzanck Prep reveals multinucleated giant cells & Intranuclear inclusion bodies. Viral Culture Serology Direct Fluorescent Antibodies Treatment: Acyclovir (Zovirax) Valacyclovir (Valtrex) Famciclovir (Famvir) Trifluridine Eye Drops for Corneal Infections Prevention: Condom Use 35 Varicella-Zoster Virus: causes 2 diseases: Varicella aka Chickenpox Herpes Zoster aka Shingles Varicella (Chickenpox) is usually a disease of children. after resolution the V-Z virus remains latent in the sensory ganglia. later in life, reactivation can cause the second disease called Herpes Zoster (Shingles). after a stress event or due to decreased cellularimmunity, the V-Z virus migrates out along sensory nerve paths and causes vesicles typically along a dermatomal distribution (almost always unilaterally). 36

13 Varicella-Zoster Virus: Varicella (Chickenpox): highly contagious, infecting up to 90% of those exposed. occurs in epidemics, usually during winter and spring and involves children who have not previously been exposed. about 90% of the general adult population have contracted the V-Z virus in childhood. Transmission by: aerosolized respiratory secretions (cough, sneeze, etc...) contact with ruptured vesicles 37 Varicella-Zoster Virus: Varicella (Chickenpox) Symptoms: 2-week incubation period: virus infects the respiratory tract and replicates for a 2-week period, followed by viremia (viral dissemination in the bloodstream). Fever and Headache develop Rash: the vesicles first erupt on the trunk and face, and then spread to involve the entire body (including the mucus membranes). the skin vesicles that form are described as dew on a rose petal: a red base with a fluid-filled vesicle on top. the fluid becomes cloudy, the vesicles rupture, and the lesions scab over. All will scab over in about 1 week. multiple vesicles arise in patches (crops), and one crop will form as another crop scabs over. Thus, there are vesicle lesions at different stages of development and resolution!!! 38 Varicella-Zoster Virus: Varicella (Chickenpox) the Rash: patients are infectious until all their lesions scab over. 39

14 Varicella-Zoster Virus: Diagnostics: Tzanck Prep reveals multinucleated giant cells & Intranuclear inclusion bodies. Clinical appearance of rash is all that is needed in most cases. No labs needed. Treatment: Acyclovir (Zovirax) Valacyclovir (Valtrex) Famciclovir (Famvir) Zoster Immune Globulin: only useful if given within days of exposure... NOT after rash develops. Prevention: Chickenpox Vaccine 40 Zoster (Shingles): following a stressed state or lowered cell-mediated immunity, the latent V-Z virus in the sensory ganglion begins to replicate and migrate to the peripheral nerves. painful, burning lesions develop over a specific sensory dermatome

15 Epstein-Barr Virus (EBV): Mononucleosis: in mononucleosis, EBV infects the human B-cells. once internalized, EBV will change the infected cell so that it does NOT follow normal growth controls... thus it acts as a malignant (cancer) cell. these changed or transformed cells proliferate and pass on copies of the EBV DNA to their progeny. the EBV DNA remains in the latent state as multiple copies of circular DNA. in some cells, the EBV activates and proliferates, and cell lysis with viral release occurs. EBV infected cells normally will be destroyed by a heathy immune system and a disease such as mononucleosis will resolve. 43 Mononucleosis: Transmission: Intimate Contact from asymptomatic shedders of CMV (kissing, etc...). Diagnosis: Elevated atypical lymphocytes (white blood cells). IgM antibodies against the viral capsid antigens. blood has heterophile antibodies against EBV:» Monospot Test agglutinates sheep RBCs. Symptoms: Fever & Sore Throat Severe Lethargy (tiredness) Lymphadenopathy (large lymph nodes) Splenomegaly (large spleen)» NO Contact Sports for months (risk of splenic rupture) Treatment: Supportive 44 DNA Viruses: PAPOVAviridae Human Papilloma Virus: Warts: some strains of HPV grow well in skin. some strains grow well in only certain areas of the body. common wart (HPV types 1, 2, 4, and 7) genital wart (HPV types 6, 11, 16, 18, and others) laryngeal wart (HPV types 6, 11) Cervical Cancer (HPV types 16, 18) warts are benign (non-cancerous) proliferations of the keratinized squamous epithelium. most warts spontaneously resolve in 1 to 2 years. 45

16 DNA Viruses: PAPOVAviridae Human Papilloma Virus: Wart Treatment: Liquid Nitrogen to freeze them off (Best Method) Surgical Excision Electrosurgery (laser ablation) Podophyllin: for genital warts HPV Prevention: HPV vaccine with Gardasil versus HPV types 6, 11, 16 and shots over 6 months and recommended for ages 9 to 26 years Other HPV facts: HPV DNA can be found in normal appearing tissue around the wart. many warts resolve spontaneously in 1 to 2 years. 46 DNA Viruses: HEPADNA viridae Hepatitis B Virus (HBV): only hepatitis caused by a DNA virus. causes acute and chronic hepatitis. Transmission: Blood Transfusion (rare) Needle Sticks Sexual Across the Placenta (VERTICAL transmission) Diagnosis via Serology: HB surface Antigen: present in acute or chronic disease. anti-hb surface Antigen: Immunity (protection) IgM anti-hb core Antigen: New infection IgG anti-hb core Antigen: Old infection HB envelope Antigen: High Infectivity anti-hb envelope Antigen: Low Infectivity 47 DNA Viruses: HEPADNA viridae Hepatitis B Virus (HBV): Prevention: HBV recombinant vaccine. Treatment: Interferon analogs Nucleoside analogs Lamivudine Adefovir Entacavir 48

17 DNA Viruses: POX viridae Smallpox: is structurally the most complex of all known viruses. it is brick-shaped the DNA is organized into a dumbbell-shape with structural proteins. surrounded by 2 envelopes lateral bodies only DNA virus to replicate in the host cell s cytoplasm. 49 DNA Viruses: POX viridae Smallpox: Transmission: Highly contagious via droplet spread (cough, sneeze). NO animal reservoirs... ONLY infects humans. Symptoms: lesions similar to chickenpox but are: deeper in the skin harder surface all lesions develop at the same time lesions more common on the extremities often the lesions are umbilicated (central depression). Treatment: no known treatment. 30% died. 50 DNA Viruses: POX viridae Smallpox: Vaccination: routine vaccination stopped in the USA in vaccination of select military members & first-responders in last case of smallpox world-wide was in Edward Jenner in 1796 used inoculations from cowpox to create the first vaccine. modern vaccine called vaccinia from Latin vacca which means cow. those vaccinated can spread the virus to other parts of their body or to others by direct contact of the injection site. 51