Virology 3 Flashcards
5 Distinct Hepatitis Viruses
- hepatitis A virus • ______virus/___ ____ virus
- hepatitis B virus • ______virus/____ ____ virus
- hepatitis C virus • ___virus/___ ___virus
- hepatitis D virus (delta agent) • ____-like/___ ____
- hepatitis E virus • ____-like/___ ___ virus
5 Distinct Hepatitis Viruses
- hepatitis A virus • picornavirus/naked RNA virus
- hepatitis B virus • hepadnavirus/enveloped DNA virus
- hepatitis C virus • flavivirus/enveloped RNA virus
- hepatitis D virus (delta agent) • viroid-like/enveloped RNA
- hepatitis E virus • calicivirus-like/naked RNA virus
Characteristics of HAV
- picornavirus
- ____ to pH ___, ____solvents, detergents, saltwater, groundwater, drying, temperature
- inactivated by ___, ____, ___ ___
- Naked
Characteristics of HAV • picornavirus • stable to pH 1.0, organic solvents, detergents, saltwater, groundwater, drying, temperature • inactivated by chlorine, formalin, UV radiation • Naked
HAV Infection
- spread by ___-___ route; ___/____ outbreaks; dirty hands can spread it in food service industry
- ____ onset
- ____ disease
- no___ ___ or___ ___
- Symptoms are ___, ___, ___, ____ of ___, ___ ___
- ___–icteric phase (___% of adults; ____% of kids)
- Skin turns yellow • In darker people you see It in the sclera of their eyes
- symptoms due to___ ___ ___ ____
- immune response fighting off infection in the liver.
- Liver damage as a result of this but its totally___ ___ and goes away pretty quickly
- Recall: Enveloped virus is less stable because derived from cell membrane. Liquid. Requires cell in which to live. Generally not transmitted by door handles, they don’t survive very long in environment. • Naked: Protein is stable
HAV Infection • spread by fecal-oral route; food/waterborne outbreaks; dirty hands can spread it in food service industry • abrupt onset • mild disease • no chronic infection or carrier states • Symptoms are fever, fatigue, nausea, loss of appetite, abdominal pain • jaundice–icteric phase (>70% of adults; 10-20% of kids) • Skin turns yellow • In darker people you see It in the sclera of their eyes • symptoms due to immune-mediated liver damage • immune response fighting off infection in the liver. • Liver damage as a result of this but its totally self resolving and goes away pretty quickly • Recall: Enveloped virus is less stable because derived from cell membrane. Liquid. Requires cell in which to live. Generally not transmitted by door handles, they don’t survive very long in environment. • Naked: Protein is stable
Pathogenesis of HAV
___ Acquisition→Crosses ___→ ___→ ___→ ___→ ___ (____ virus particles/mL)
Pathogenesis of HAV Oral Acquisition→Crosses Intestines→ Blood→ Liver→ Bile→ Stool (10^8 virus particles/mL)
HAV Epidemiology
- HAV causes ___% of acute hepatitis
- most infected people are infectious____ symptoms occur • They don’t know it and they can spread it
- 90% of infected kids and 25-50% of infected adults have____, but ____e infections • Don’t get sick but can spread virus
- outbreaks originate from a ___ ____ • All the pomegranate seeds in a shipment are contaminated
HAV Epidemiology • HAV causes 40% of acute hepatitis • most infected people are infectious before symptoms occur • They don’t know it and they can spread it • 90% of infected kids and 25-50% of infected adults have inapparent, but productive infections • Don’t get sick but can spread virus • outbreaks originate from a common source • All the pomegranate seeds in a shipment are contaminated
Reported number of cases Has been ____ since 2000
Reported number of cases Has been decreasing since 2000
Treatment and Control of HAV
- ___ ___ ____ 80-90% effective • For ___ ____ prophylaxis • Basically, ___ to the virus • ____ type of immunization
- ___ of ___ ___
- frequen ___ ___
- vaccine (licensed in 1995) • Havrix recommended by ___ yr of age • ___ serotype • So easy to immunize against • infects __ ____ • Twinrix combo vaccine for age 18+ • Get booster before college
Treatment and Control of HAV • immune serum globulin 80-90% effective • For post exposure prophylaxis • Basically, Ab to the virus • Passive type of immunization • chlorination of drinking water • frequent hand-washing • vaccine (licensed in 1995) • Havrix recommended by 1 yr of age • only one serotype • So easy to immunize against • infects only humans • Twinrix combo vaccine for age 18+ • Get booster before college
HBV—Pathogenesis
- Much more complex virus
- You see it occurring in ___ ___ in the blood o Filamentous o Complete viral particle
- Lots of ___ and ___ Ag
- Infection with HBV→ increased levels of ___ ___ ___
- In an immune person, ___ will block any complications from that
- Most people will have symptoms and it will ___ ___
- During process of resolving infection, virus will spread by ____ • Will be in saliva, semen, vaginal secretions, blood and mothers milk
- Here again you can prevent spread of the disease with ___
- Problem is people who become ____ infected with Hep B
o Not much of a problem in the ____, vaccine world but plenty of people still carry the virus • Virus can be transmitted ___, ___, ___ and ___ ___
HBV—Pathogenesis • Much more complex virus • You see it occurring in many forms in the blood o Filamentous o Complete viral particle • Lots of enzymes and core Ag • Infection with HBV→ increased levels of HBV surface Ag • In an immune person, Ab will block any complications from that • Most people will have symptoms and it will resolve infection • During process of resolving infection, virus will spread by viremia • Will be in saliva, semen, vaginal secretions, blood and mothers milk • Here again you can prevent spread of the disease with Ab • Problem is people who become chronically infected with Hep B o Not much of a problem in the developed, vaccine world but plenty of people still carry the virus • Virus can be transmitted neonatally, blood, sexually and thru drug abuse
HBV Infection/Epidemiology
- parenteral (___ borne) and ___ ____ (thru mucous membranes)
- ____, insidious onset→ not as ___ as HAV
- fever, fatigue, loss of appetite, nausea, vomiting, abdominal pain, __ ___, ___ ___, jaundice • Signs/symptoms pretty much the same as HAV
- Can result in ___ ___ and ___ ___
- 800,000-1.4 million in U.S. have chronic infection
- 350 million worldwide have chronic infection
- 786,000 deaths annually worldwide from HBV-related liver disease
- Carriers can transmit it
- Associated with ___ ___ ____
- Liver is a regenerative tissue • As SC continue to replicate they become more sus to other damage to their DNA and you can get the formation of a tumor
HBV Infection/Epidemiology • parenteral (blood-borne) and sexual transmission (thru mucous membranes) • slow, insidious onset→ not as acute as HAV • fever, fatigue, loss of appetite, nausea, vomiting, abdominal pain, dark urine, joint pain, jaundice • Signs/symptoms pretty much the same as HAV • Can result in chronic infection and carrier state • 800,000-1.4 million in U.S. have chronic infection • 350 million worldwide have chronic infection • 786,000 deaths annually worldwide from HBV-related liver disease • Carriers can transmit it • Associated with primary hepatocellular carcinoma • Liver is a regenerative tissue • As SC continue to replicate they become more sus to other damage to their DNA and you can get the formation of a tumor
Reported number of cases
____a huge problem in US anymore bc we have immunized against it.
Reported number of cases Not a huge problem in US anymore bc we have immunized against it.
HBV Carriers—
Worldwide Prevalence
Areas where hepatocellular carcinoma is also very prevalent
Developed world, ___________
HBV Carriers—Worldwide Prevalence Areas where hepatocellular carcinoma is also very prevalent Developed world, its not a problem
Transmission of HBV Modes
- ____ with an infected partner
- _____ drug use that involves sharing needles, syringes, or prep equipment
- ___ to an___ ___.
contact with ___ or ___ ___ of an infected person
- needle sticks or sharp instrument exposures
- sharing items like ___ or____ with an infected person
Risk Groups
- ___born to infected mothers
- __ ___ of infected persons
- sexually ____ individuals
- ___ who have sex with ___
- injection __ ___
- ___ ___ of persons with chronic HBV infection
- ___ __ ___and public safety workers at risk for occupational exposure to blood or blood-contaminated body fluids
•_____ patients
• residents and staff or facilities for the ___ ___
___ to ____with intermediate or high prevalence of HBV infection
Transmission of HBV Modes • sex with an infected partner • injecting drug use that involves sharing needles, syringes, or prep equipment • birth to an infected mother • contact with blood or open sores of an infected person • needle sticks or sharp instrument exposures • sharing items like razors or toothbrushes with an infected person Risk Groups • infants born to infected mothers • sex partners of infected persons • sexually promiscuous individuals • men who have sex with men • injection drug users • household contacts of persons with chronic HBV infection • health care workers and public safety workers at risk for occupational exposure to blood or blood-contaminated body fluids • hemodialysis patients • residents and staff or facilities for the developmentally disabled • travelers to countries with intermediate or high prevalence of HBV infection
HBV Treatment/Vaccines
- ___ ____inhibitors
- ___ __ ___• Amped up with polyethylene glycol that makes it stick together better and be more effective and gives ___ ___
- vaccination
- ___ ___ Hep B vaccines (2)
- Vaccine used to be made with Hep B surface Ag that was purified from the plasma of infected people, but now we have the ____ vaccine
- ____ Vaccines (3)
HBV Treatment/Vaccines • reverse transcriptase inhibitors • pegylated α-interferon • Amped up with polyethylene glycol that makes it stick together better and be more effective and gives higher dose • vaccination • Single Ag Hep B vaccines (2) • Vaccine used to be made with Hep B surface Ag that was purified from the plasma of infected people, but now we have the recombinant vaccine • Combo Vaccines (3)
Hepatitis C Virus (HCV)
• Flavivirus—identified in ___; ___ genotypes o Analogous to west nile and others that are arthropod transmitted, but it is not transmitted that way
o Knowing which genotype person has can direct treatment
- Most infected people get ____ disease as opposed to ____ disease
- establishes ___-____, _____ infections leading generally to _____ disease (70%)
- accounts for ____% of cases of non-A non-B hepatitis; genotype ___most prevalent
- HCV chronic disease (3.2 million Americans) ___ prevalent than ___ ____ disease (800,000-1.4 million Americans)
- prevalence worldwide is 2%=123,000,000 people
- ___ ___ for ___ ____
o Bc so many people become chronically infected, their liver gets destroyed
• most ___ ___ ___ ____ in U.S. • The real problem in this family
Hepatitis C Virus (HCV) • Flavivirus—identified in 1989; 6 genotypes o Analogous to west nile and others that are arthropod transmitted, but it is not transmitted that way o Knowing which genotype person has can direct treatment • Most infected people get CHRONIC disease as opposed to acute disease • establishes non-cytolytic, persistent infections leading generally to chronic disease (70%) • accounts for 90% of cases of non-A non-B hepatitis; genotype 1 most prevalent • HCV chronic disease (3.2 million Americans) more prevalent than HBV chronic disease (800,000-1.4 million Americans) • prevalence worldwide is 2%=123,000,000 people • leading indication for liver transplantation o Bc so many people become chronically infected, their liver gets destroyed • most common blood-borne infection in U.S. • The real problem in this family
Pathogenesis of HCV
- viremia lasts ____ months in acute infection o During that time they are infectious. o This is longer duration that HAV, HBV acute
- viremia lasts ___ years in persistent infection
- ____ (immune response) leads to ___ ___ (liver)
- continual ___ ___ and induction of cell growth during __ ___ predisposes to liver cancer development
- _____ are ___ ____ so difficult to make a vaccine
- ____ ___ ___ blocks ___ of ___ ___ ___o Virus makes serine protease
- ____ _____ may prevent HCV from blocking interferon (Used in treatment of HCV)
Pathogenesis of HCV • viremia lasts 4-6 months in acute infection o During that time they are infectious. o This is longer duration that HAV, HBV acute • viremia lasts 10 years in persistent infection • CMI (immune response) leads to tissue damage (liver) • continual liver repair and induction of cell growth during chronic infection predisposes to liver cancer development • Antibodies are not protective so difficult to make a vaccine • HCV serine protease blocks activation of interferon regulatory factor o Virus makes serine protease • Protease inhibitors may prevent HCV from blocking interferon (Used in treatment of HCV)
HCV—
Transmission Modes
- ___ __ ____ (most common)
- needlestick injuries in __ ___ settings
- ____ to an HCV-infected mother
- inefficient modes
- ___ with an HCV-infected person
- ____ personal items contaminated with infectious blood
- invasive health care____
Risk Groups
- current or former __ ___ ___
- recipients of donated blood, blood products, and organs prior to ____ • It took us some time to get a test to screen for HCV
- ___ ___ ___ at risk for occupational exposure to blood or blood-contaminated body fluids
- persons with ____ infection • Bc of suppresed immune system
- ___ ___ to HCV-positive mothers
HCV—Transmission Modes • injection drug use (most common) • needlestick injuries in health care settings • birth to an HCV-infected mother • inefficient modes • sex with an HCV-infected person • sharing personal items contaminated with infectious blood • invasive health care procedures Risk Groups • current or former injection drug users • recipients of donated blood, blood products, and organs prior to 1992 • It took us some time to get a test to screen for HCV • health care workers at risk for occupational exposure to blood or blood-contaminated body fluids • persons with HIV infection • Bc of suppresed immune system • children born to HCV-positive mothers
Reported number of Acute HCV cases
____ for awhile but its been going __ ___
Still a major problem bc we have no way to __ ___other than being careful.
Reported number of Acute HCV cases Dipped for awhile but its been going back up Still a major problem bc we have no way to prevent transmission other than being careful.
Diagnosis and Control of HCV
- diagnosis based on detection of ____; seroconversion in ____ weeks; antibody ___ __ ___ in viremic people making serologic diagnosis of acute disease difficult
- Ab aren’t ___ but they are still an ___
- People will generally ____ over time but people who have viremia do not always have Ab, so difficult to diagnose using serology.
- ___ ___in serum better indicator • Test to look for RNA of virus in the serum
- controlled by ____ of blood supply and avoidance of ___ __ ___
Diagnosis and Control of HCV • diagnosis based on detection of antibody; seroconversion in 7-31 weeks; antibody not always present in viremic people making serologic diagnosis of acute disease difficult • Ab aren’t protective but they are still an indicator • People will generally seroconvert over time but people who have viremia do not always have Ab, so difficult to diagnose using serology. • virion RNA in serum better indicator • Test to look for RNA of virus in the serum • controlled by screening of blood supply and avoidance of high-risk behaviors
Treatment for Hepatitis C
- Considerations
- HCV ____
- __ ___→Serum RNA
- past ___
- degree of ___ ___
____status
- Drugs—combination therapies
- __ ___
- __ ___
- __ ___ • Interfere with repl of viral NA
- ___% cure rate • newer drugs very ____ Some say they are 90% effective in curing
Treatment for Hepatitis C • Considerations • HCV genotype • viral load→Serum RNA • past treatment • degree of liver damage • transplant status • Drugs—combination therapies • pegylated interferon • protease inhibitors • nucleoside analogues • Interfere with repl of viral NA • >80% cure rate • newer drugs very expensive Some say they are 90% effective in curing
Characteristics of HDV
- ___ ___genome surrounded by ___ ___
- ____ ____; essential for ____viru
s • Not much of a problem now bc most people are vaccinated against ____
- Can only replicate in person who has __ ___
- It’s a different type of genome and has its own Ag (Delta Ag) but it’s in a coat of HBV surface Ag. That’s essential for packaging the virus. So you cant get HDV alone if you don’t have HBV
Characteristics of HDV • ss RNA genome surrounded by delta antigen • HBsAg envelope; essential for packaging virus • Not much of a problem now bc most people are vaccinated against HBV • Can only replicate in person who has HBV infection • It’s a different type of genome and has its own Ag (Delta Ag) but it’s in a coat of HBV surface Ag. That’s essential for packaging the virus. So you cant get HDV alone if you don’t have HBV
Pathogenesis of HDV
- replicates and causes disease only in those with active__ ___ •___-infection •___infection
- more ___, ___progression in HBV carriers
- causes direct ____ and __ ___
- immunization against HBV protects against HDV infection
In people who are carriers of HBV who then become infected with HDV, you can have more rapid, severe disease and it can be fatal
Pathogenesis of HDV • replicates and causes disease only in those with active HBV infection • co-infection • superinfection • more rapid, severe progression in HBV carriers • causes direct cytotoxicity and liver damage • immunization against HBV protects against HDV infection In people who are carriers of HBV who then become infected with HDV, you can have more rapid, severe disease and it can be fatal
Characteristics of HEV • calicivirus-like • Small naked RNA viruses
- ______spread like HAV • ___ ___ ___
- causes only ___ disease • ___ onset
- mild disease like HAV in normal patients, ____mortality than HAV
- We don’t know why
- Few people die from either HAV and HEV infection
____ prevalence in developed world, but nearly 3 million cases in developing world • A lot like HAV but member of different virus family (calicivirus)
Characteristics of HEV • calicivirus-like • Small naked RNA viruses • fecal-oral spread like HAV • contaminated drinking water • causes only acute disease • abrupt onset • mild disease like HAV in normal patients, higher mortality than HAV • We don’t know why • Few people die from either HAV and HEV infection • low prevalence in developed world, but nearly 3 million cases in developing world • A lot like HAV but member of different virus family (calicivirus)
- HIV ___ ____ virus
- envelope contains ___ ___; acquired by ____
- capsid contains ____ identical copies of ___ strand RNA
- 10-50 copies of __ ___and ___ o In order to replicate it has to make a ___copy of the RNA so it has its own RT
- 2 cellular_____
- Tests to diagnose and moniter level of infection are directed at:
o ____—virion ___ protein
o___—___ protein
o ___—marker of a___ ___n
• Extremely important still • Complex virus
• enveloped RNA virus • envelope contains viral glycoproteins; acquired by budding • capsid contains two identical copies of + strand RNA • 10-50 copies of reverse transcriptase and integrase o In order to replicate it has to make a DNA copy of the RNA so it has its own RT • 2 cellular tRNA’s • Tests to diagnose and moniter level of infection are directed at: o gp120—virion attachment protein o gp41—fusion protein o p24—marker of active replication • Extremely important still • Complex virus
HIV Replication: RNA→ DNA→ RNA
- Fusion of HIV to ___ __ ___
___ binds ___ Ag
Co receptors ___ or ____
Can infect mononuclear blood cells and lymphocytes
- HIV ___, __, ____ and other viral proteins enter the host cell
- Viral ___ is formed by __
- Viral DNA is transported across the nucleus and ____ into the host DNA
- New viral RNA is used as genomic RNA and to make___ ___s for assembly
- New viral RNA and proteins move to the __ ___e and a new mature, HIV forms
- The virus matures by ____ releasing individual HIV proteins
All these enzymes are good targets for drugs
HIV Replication: RNA→ DNA→ RNA 1. Fusion of HIV to host cell surface Gp120 binds CD4 Ag Co receptors CCR5 or CXCR4 Can infect mononuclear blood cells and lymphocytes 2. HIV RNA, RT, integrase and other viral proteins enter the host cell 3. Viral DNA is formed by RT 4. Viral DNA is transported across the nucleus and integrates into the host DNA 5. New viral RNA is used as genomic RNA and to make viral proteins for assembly 6. New viral RNA and proteins move to the cell surface and a new mature, HIV forms 7. The virus matures by protease releasing individual HIV proteins All these enzymes are good targets for drugs
