Transcript Hepatitis - Arkansas State University

Remaining viruses
• Hepatitis viruses
– Hep A, B, and C.
• Picornaviruses and common cold viruses
• Influenza and the MMR group
• HIV and sexually transmitted viruses
• Mosquito-borne viruses of Arkansas
• Sort of a mixture of groupings by type and
groupings by disease.
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Hepatitis
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• 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.
Hepatitis B
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• 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
Hep B continued
• 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 now recommended
– Because of bad result of early infection and great
danger of liver damage, liver cancer.
– Recombinant vaccine.
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General model for viral carcinogenesis
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Hepatitis A virus
• 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
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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
Other viral Hepatitis: D, E, F, G, …more?
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A molecular biology lesson
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• DNA is copied faithfully
– DNA polymerase has 3’ to 5’ exonuclease activity, a
“backspace key” which deletes mistakes.
– Other mechanisms exist to maintain fidelity.
• RNA fidelity is not maintained
– RNA polymerase does not backspace
– Methods for monitoring RNA don’t exist
• Many RNA viruses show high mutation rate
– Many variants, immunity difficult.
Picornaviruses
• Small RNA viruses (“pico” = very small)
– About 25 nm, near the size of a ribosome
– Two kinds
• Enteric viruses
– includes Hepatitis A and polio
• Only some cases of polio result in paralysis
– Cause of many cases of “stomach flu”
• Rhinoviruses: major cause of common cold
– Rhino means nose
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The Common cold
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• 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
– Coronavirus (best known cousin causes SARS)
– Adenovirus (DNA virus), some serotypes cause GI
infections
Orthomyxovirus
• Influenza: a serious respiratory disease
– 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
– Shift: major mixing of RNAs, whole new virus.
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View of flu
http://www.astrosurf.org/lombry/Bio/virus-influenza.jpg
http://www-micro.msb.le.ac.uk/3035/3035pics/flusection.jpg
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Nature of influenza
• Attack on respiratory tract
– Kills ciliated epithelial cells, allows bacterial
infections.
– Release of interferon from cells causes symptoms
• H antigen (hemagglutinin) for attachment
– That it agglutinates RBCs is an artifact
• N antigen: neuraminidase
– Cuts of the sugar on the glycoprotein receptor
– Allows new virions to escape from cell without
getting stuck
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Role of H and N spikes and host cell
polysaccharide
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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 $
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HIV: Human Immunodeficiency Virus
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• Host range
– Main types of cells infected: T helper cells and
dendritic cells (including macrophages, microglia)
• Have CD4 and CCR5 glycoproteins on surface
• Infection process
– RNA is copied into cDNA by reverse transcriptase
– cDNA inserts into host chromosome
– New RNA made
– Protein precursor made, then processed; assembly
occurs
– Virions bud through cell membrane
Disease process
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• Chronic infection
– T cells continually made, continually destroyed
– Eventually, host loses
• AIDS diagnosis:
– Acquired Immuno Deficiency Syndrome
• CD4 cell count below 200/µl;
• opportunistic infections
• Examples of opportunistic “infections”
– Pneumocystis carinii pneumonia (PCP pneumonia)
– Kaposi’s sarcoma; Tuberculosis; several others
Prevention and Treatment
• Prevention is easy
– Practice monogamous sex, avoid shared needles
– HIV cannot be spread by casual contact, skeeters
• Drug treatment
– Nucleoside analogs such as AZT
– Protease inhibitors prevent processing of viral
proteins
Nifty animation at:
http://www.hopkins-aids.edu/hiv_lifecycle/hivcycle_txt.html
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Sexually transmitted viral diseases
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• Herpes simplex II; Hepatitis B; HIV
• Papilloma virus
– Cause of warts, in this case, genital warts
– Virus tricks cell into preparing for cell division
• Protein E7 binds to pRB
– Leads to greater susceptibility to cancer, particularly
cervical cancer
• Especially those viral strains that aren’t good at
causing actual warts
Paramyxoviruses
• Family of RNA viruses related to the influenza family
• Measles- Rubeola
– Childhood disease, still a global cause of illness
– Begins with respiratory infection, then fever and cold, then
systemic with characteristic rash
– Serious neurological complications in small percentage
– Series of MMR vaccine; killed vaccine was ineffective
• Mumps
– Infection in URT and nodes, then viremia
– Infection of glands, especially parotitis
• Orchitis, meningitis, deafness are complications
– Recent outbreaks in UK, Iowa. MMR vaccine
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Paramyxoviruses-2
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• Respiratory syncytial virus
– Respiratory disease of children, no vaccine
– Infants under 6 months may require hospitalization
•Rubella – German
Measles, a Togavirus
•was once the major viral
cause of birth defects.
•Mild, kills few cells.
•MMR vaccine important
Arkansas Arboviruses
• Not an official taxonomic group, but short for
“arthropod-borne”
– Includes Flaviviruses, Togaviruses, and others.
– Zoonotic, spread from animals to people by
arthropod vectors, especially mosquitoes.
• Reservoirs may be birds, various mammals
– Result in two main types of illnesses
• Encephalitis, inflammation of the brain
• Hemorrhagic fever: high fever with bleeding
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Arkansas Arboviruses
• Encephalitis: spread by skeeters
– Eastern Equine encephalitis;
• Togavirus; summer 2005, outbreak in NE US
• Also infects, kills horses. Most dangerous.
– St. Louis encephalitis,
• Flaviviral diseases; Human disease.
• Usually not serious.
– West Nile virus
• Flavivirus; imported to US, spread from NYC
• Disease mostly in young and elderly
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