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
HIV- Pathogenesis
- primary target cells are ____ cells and cells of the ____ lineage
- ___ infection of CD4+ T cells • Infects, virus replicates and kills the cell→ leads to low levels of CD4 • ____, ___-level ____ infection of macrophage lineage cells; _____ of the virus • Reservoir: Macrophage • Consistent low level of infection • Replicates
- Virus can cause ___ ____ (syncytia) formation
- alteration of T-cell and macrophage function
HIV- Pathogenesis • primary target cells are CD4+ T cells and cells of the macrophage lineage • lytic infection of CD4+ T cells • Infects, virus replicates and kills the cell→ leads to low levels of CD4 • persistent, low-level productive infection of macrophage lineage cells; reservoir of the virus • Reservoir: Macrophage • Consistent low level of infection • Replicates • Virus can cause multinucleated cells (syncytia) formation • alteration of T-cell and macrophage function
Staging of HIV Infection
- Acute HIV Infection • develops ___ weeks after infection • __ __e symptoms—fever, headache, rash • virus multiplies ___ and ____ hroughout the body • CD4+ cells ____ • ___ risk for transmission • Most don’t know that they have HIV
- Chronic HIV Infection • period of __ ___ • virus replicates at ___ ___ • usually ____ • transmission ____
- AIDS • Sus to the___ ____ that kill people with HIV • Sus to ___ ___ (like KS) • CD4 count less than ____ cells/mm3
Staging of HIV Infection • Acute HIV Infection • develops 2-4 weeks after infection • flu-like symptoms—fever, headache, rash • virus multiplies rapidly and spreads throughout the body • CD4+ cells destroyed • highest risk for transmission • Most don’t know that they have HIV • Chronic HIV Infection • period of clinical latency • virus replicates at low levels • usually asymptomatic • transmission possible • AIDS • Sus to the opportunistic infections • that kill people with HIV • Sus to certain cancer (like KS) • CD4 count less than 200 cells/mm3
Time Course of HIV Infection
CD4 count ____s at beginning, then may ____ a little. During clinical latency, it just ___ ____
HIV RNA copies: After infection get a __ ___ in the viral load and then it comes ____ and then goes back ___p when have ___
Time Course of HIV Infection CD4 count drops at beginning, then may increase a little. During clinical latency, it just slowly decrease. HIV RNA copies: After infection get a huge boost in the viral load and then it comes down and then goes back up when have AIDS.
HIV Infection—Risk Factors
- engaging in ____d sex
- ___ sex more risky than vaginal sex
- having another ___—genital herpes, gonorrhea, chlamydia
- intravenous ___ ___ involving sharing of needles and syringes
lack of ____ increases risk of heterosexual transmission
- exposure to the virus as a ___ or ____before or during birth or through ___from a mother infected with HIV
- receipt of a blood transfusion or clotting factor in the United States anytime from 1978 to ____
HIV Infection—Risk Factors • engaging in unprotected sex • anal sex more risky than vaginal sex • having another STD—genital herpes, gonorrhea, chlamydia • intravenous drug use involving sharing of needles and syringes • lack of circumcision increases risk of heterosexual transmission • exposure to the virus as a fetus or infant before or during birth or through breastfeeding from a mother infected with HIV • receipt of a blood transfusion or clotting factor in the United States anytime from 1978 to 1985
HIV—Transmission •
HIV __ ___ for very long outside of the body. (envelope virus)
- HIV cannot be transmitted through __ ___ __ such as using a toilet seat, sharing food utensils or drinking glasses, shaking hands, or through ____
- HIV can only be transmitted from person to person, not through ___ or __ ___.
- People infected with HIV who are taking_____ therapy can still __ ____ through unprotected sex and sharing needles and syringes. (Virus not completely eliminated from their body)
HIV—Transmission • HIV cannot survive for very long outside of the body. (envelope virus) • HIV cannot be transmitted through routine daily activities such as using a toilet seat, sharing food utensils or drinking glasses, shaking hands, or through kissing. • HIV can only be transmitted from person to person, not through animals or insect bites. • People infected with HIV who are taking antiretroviral therapy can still infect others through unprotected sex and sharing needles and syringes. (Virus not completely eliminated from their body)
HIV and Saliva
Only a small minority of HIV-infected individuals harbor the virus in ___ ___
HIV virions cannot live in a __ ___ state in saliva (has to be in a cell to live)
(<1 infectious particle/ml of mixed saliva).
____ antibodies to p24, gp120, gp160 may neutralize infectivity.
____ entrap virus.
___ ___ __ ____ may block ___ ___ HIV ___
HIV loses infectivity when exposed to ___ saliva for ___ min.
Animal studies have shown that it is not possible to transmit HIV by ___ ___ to___ ___in contrast to vaginal mucosa.
HIV and Saliva
Only a small minority of HIV-infected individuals harbor the virus in whole saliva.
HIV virions cannot live in a cell-free state in saliva (has to be in a cell to live)
(<1 infectious particle/ml of mixed saliva).
IgA antibodies to p24, gp120, gp160 may neutralize infectivity.
Mucins entrap virus.
Salivary leukocyte protease inhibitor (SLPI) may block cell surface HIV receptors.
HIV loses infectivity when exposed to mixed saliva for 30 min.
Animal studies have shown that it is not possible to transmit HIV by surface application to oral mucosa in contrast to vaginal mucosa.
HIV—Treatment
- ____ HIV drugs on the market;____of possible combinations
- _____ _______ ___ ____ inhibitors Incorporate into viral DNA
- non-____e ___ ____e inhibitors
- ____ inhibitors prevent___ ___ from forming
- ____ inhibitors
____ ____ inhibitors
- ____-___ inhibitors
- ____ inhibitors • ____ inhibitors Prevent egress of virus from the cell
- There are problems with ___ ___e
- current therapy—____ combination of 3 or 4 drugs
HIV—Treatment • >20 HIV drugs on the market; hundreds of possible combinations • nucleoside/tide analogue reverse transcriptase inhibitors Incorporate into viral DNA • non-nucleoside reverse transcriptase inhibitors • fusion inhibitors prevent multinucleated cells from forming • integrase inhibitors • ribonucleotide reductase inhibitors • zinc-finger inhibitors • protease inhibitors • maturation inhibitors Prevent egress of virus from the cell • There are problems with drug resistance • current therapy—HAART; combination of 3 or 4 drugs
HIV Infection—Oral Manifestations
- ____:
- ____
- ____
- ___ ___
- Immunosuppressed
- __ ___(caused by EBV)
- _____ disease
- ___ ___ ___ • Red along the gingiva
- ___ ____ • Bleeding, necrotic
- ___ ___ ___
- ____ ___ (HHV8)
- ___ __ ____
Can see these in people who don’t have HIV infection but more severe in those that do
HIV Infection—Oral Manifestations • candidiasis • erythematous • pseudomembanous • angular cheilitis • Immunosuppressed • hairy leukoplakia (caused by EBV) • periodontal disease • linear gingival erythema • Red along the gingiva • necrotizing gingivostomatitis • Bleeding, necrotic • necrotizing ulcerative periodontitis • Kaposi’s sarcoma (HHV8) • non-Hodgkin lymphoma Can see these in people who don’t have HIV infection but more severe in those that do
• HPV
___ capsid
- 55 nm in diameter
- ____-stranded ___ ___; __ genes and a ___ ___
- over____ genotypes cloned from clinical lesions
- Most viruses we talk about serotypes, bc they have structural Ag that allow you to differentiate them. • All HPV have ___ __ ___ • Distinguished by differences in their DNA
- cellular target—___ cell or_____ of ___ or___ ___
- induce epithelial cell ____
- ____
- _____t (with other co-factors helping to drive malignant conversion)
• naked capsid • 55 nm in diameter • double-stranded circular DNA; 8 genes and a regulatory region • over 150 genotypes cloned from clinical lesions • Most viruses we talk about serotypes, bc they have structural Ag that allow you to differentiate them. • All HPV have same structural Ag • Distinguished by differences in their DNA • cellular target—epithelial cell or keratinocyte of skin or mucous membranes • induce epithelial cell proliferation • benign • malignant (with other co-factors helping to drive malignant conversion)
Prototype HPV’s
- mucosal infections
- HPV __ and HPV ___—low risk for malignant conversion
- HPV ___ and HPV ___—high risk for malignant conversion
- cutaneous infections
- HPV _, HPV _, HPV _: Cause warts
- numerous types in ____ ____ patients • affects the skin • people are immunosuppressed
- ___risk for malignant conversion
- ___ risk for malignant conversion in some parts of the body • in combo with sun exposure and other factors
Prototype HPV’s • mucosal infections • HPV 6 and HPV 11—low risk for malignant conversion • HPV 16 and HPV 18—high risk for malignant conversion • cutaneous infections • HPV 1, HPV 2, HPV 4: Cause warts • numerous types in epidermodysplasia verruciformis patients • affects the skin • people are immunosuppressed • low risk for malignant conversion • high risk for malignant conversion in some parts of the body • in combo with sun exposure and other factors
Five Groups of HPV
- Alpha: ___ and ___s infections; high and low risk types o This what we mostly concerned about
- Beta:____ infections; high and low risk types o ___ patients
- Gamma: ___ __ ___
- Mu: B___ __ ___ns
- Nu:___ __ ___
Five Groups of HPV • Alpha: mucosal and cutaneous infections; high and low risk types o This what we mostly concerned about • Beta: cutaneous infections; high and low risk types o EV patients • Gamma: benign cutaneous infections • Mu: Benign cutaneous infections • Nu: Benign cutaneous infections
HPV—Transmission/Epidemiology
- acquired by ___ ___
- disease presentation depends on ____of virus
- Virus gets in by some sort of ____
- virus persists in the ___ __ ___ and replicates in ____ _____ layers
- benign lesions (warts) often resolve ____
- HPV DNA becomes ____ into host cell DNA in associated cancers
- most common___ __ ____ the U.S.
- At least 50% of sexually active, non-vaccinated people will have genital HPV infections during their lifetime; most will clear with no symptoms
- 6 million new infections/yr in the U.S.
- 1% of sexually active adults in the U.S. have genital warts at any one time so they can transmit the virus sexually
HPV—Transmission/Epidemiology • acquired by close contact • disease presentation depends on genotype of virus • Virus gets in by some sort of abraision • virus persists in the basal cell layer and replicates in more differentiated layers • benign lesions (warts) often resolve spontaneously • HPV DNA becomes integrated into host cell DNA in associated cancers • most common sexually transmitted virus in the U.S. • At least 50% of sexually active, non-vaccinated people will have genital HPV infections during their lifetime; most will clear with no symptoms • 6 million new infections/yr in the U.S. • 1% of sexually active adults in the U.S. have genital warts at any one time so they can transmit the virus sexually
HPV—Pathogenesis
Virus infects___ ___
Viral genome is ____ there
As you get further out in the epithelium (____basal) you get ____ of the genome and cell ____. Get expression of genes important for ___ ___.
Then in the ____ layer ____ proteins (__ and ___) of virus are made and virus gets ____
Virus is released from ___ ___ layer of the epithelium thru ____ of the cells
HPV—Pathogenesis Virus infects basal layer. Viral genome is maintained there As you get further out in the epithelium (suprabasal) you get maintenance of the genome and cell proliferation. Get expression of genes important for viral replication. Then in the granular layer structural proteins (L1 and L2) of virus are made and virus gets assembled Virus is released from outer most layer of the epithelium thru sloughing of the cells
Oral HPV Infections
- You can get what are called ___ ____—caused by HPV _ and HPV ___ • lesions
- ___ ____ (common wart)—HPV _ and HPV _ • Can be seen in ___ ___ of the lip
- ____ warts (condylomas)—HPV _ and HPV __• genital warts in the ___
- ___ ___ ___—HPV __ and HPV ___ (____ types, not a malignancy, probably some genetic predisposition)
- oral warts more common in patients with ____ disease—___ HPV types may be found
- ___ ____ in children infected at birth—HPV __ and HPV __• Can obstruct the airway
- small percentage of healthy people have ____ HPV types in oral cavity
- Need lots more than just the virus for tumor to form
Oral HPV Infections • You can get what are called oral papilloma—caused by HPV 6 and HPV 11 • lesions • verruca vulgaris (common wart)—HPV 2 and HPV 4 • Can be seen in vermillion border of the lip • venereal warts (condylomas)—HPV 6 and HPV 11 • genital warts in the mouth • focal epithelial hyperplasia—HPV 13 and HPV 32 (mucosal types, not a malignancy, probably some genetic predisposition) • oral warts more common in patients with HIV disease—rarer HPV types may be found • laryngeal papillomatosis in children infected at birth—HPV 6 and HPV 11 • Can obstruct the airway • small percentage of healthy people have oncogenic HPV types in oral cavity • Need lots more than just the virus for tumor to form
Benign HPV- Induced Cutaneous Lesions
___ warts- finger, palm, nail bed
___ warts
___ warts
Benign HPV- Induced Cutaneous Lesions Hand warts- finger, palm, nail bed Plantar warts Flat warts
HPV- A Tumor Virus
In the course of forming a tumor, there are two proteins that are very important. 1) ___2) ___
Both work to keep cells ___ ____
In the cell cycle there is important protein called ___ tumor suppressor product.
In an oncogenic HPV infection, the ___ protein ___ to active form of ___, and cells can progress thru cell cycle. More sus to DNA damage.
___ causes ____ of____ (normally drives apoptosis)
HPV- A Tumor Virus In the course of forming a tumor, there are two proteins that are very important. 1) E6 2) E7 Both work to keep cells replicating uncontrollably In the cell cycle there is important protein called Rb tumor suppressor product. In an oncogenic HPV infection, the E7 protein binds to active form of Rb, and cells can progress thru cell cycle. More sus to DNA damage. E6 causes degradation of p53 (normally drives apoptosis)
HPV-Associated Cancers
- anogenital cancers • ___ • ___ • ___ • ___• ___
- oropharyngeal cancers • ___ __ __ • ____
- ___ ____ skin cancer
HPV-Associated Cancers • anogenital cancers • cervix • vulva • vagina • penis • anus • oropharyngeal cancers • base of tongue • tonsils • non-melanoma skin cancer
HPV and Cervical Cancer Progression
- Associated with about ____% of cases of cervical cancer
- HPV___ is most common. HPV__ next most common •
Virus gets into cervix by ___ ___ and infects the cells and then you get a progression of lesion from lower __ to higher grade of ___
At some point in here you get disregulation of cell cycle
• Not known why some lesions ___ and some lesions ___
HPV and Cervical Cancer Progression • Associated with about 99.9% of cases of cervical cancer • HPV16 is most common. HPV18 next most common • Virus gets into cervix by micro lesion and infects the cells and then you get a progression of lesion from lower grade to higher grade of neoplasia. At some point in here you get disregulation of cell cycle • Not known why some lesions regress and some lesions progress
HPV and Oral Cancer
- 2 subgroups of oral cancer
- HPV+
- localized to ___
- ____ of the mouth
- tend to occur in___ individuals • mostly___
- ____ prognosis
- HPV−
- generally associated with prolonged use of ___ and ___
- ____ survival rate ≈ 50%
- occur in ___ people, mostly men
HPV and Oral Cancer • 2 subgroups of oral cancer • HPV+ • localized to oropharynx • Back of the mouth • tend to occur in younger individuals • mostly men • better prognosis • HPV− • generally associated with prolonged use of alcohol and tobacco • 5 yr survival rate ≈ 50% • occur in older people, mostly men
HPV-Related Oropharyngeal Cancer—Risk Factors
• increased ____ of lifetime sexual partners
___ ___ at first sexual activity
• history of having a ___ ___ partner
HPV-Related Oropharyngeal Cancer—Risk Factors • increased number of lifetime sexual partners • younger age at first sexual activity • history of having a same-sex partner
Incidence of HPV Associated Cancers
- ___ ___is most common HPV associated infection in women
- ____ Cancer is most common HPV associated infection in men
Incidence of HPV Associated Cancers • Cervical Cancer is most common HPV associated infection in women • Oropharynx Cancer is most common HPV associated infection in men
HPV Vaccine
- Gardasil® • types __ ___ __ ___
- 16 and 18 associated with ___% of ____cancers
- 6 and 11 associated with ___% of___ ___
- Cervarix® • types __ and ___
- Gardasil-9® • FDA approved December 2014 • includes type 6, 11, 16, 18,__ ___ ___ ___and ___
HPV Vaccine • Gardasil® • types 6, 11, 16, 18 • 16 and 18 associated with 70% of genital cancers • 6 and 11 associated with 90% of genital warts • Cervarix® • types 16 and 18 • Gardasil-9® • FDA approved December 2014 • includes type 6, 11, 16, 18, 31, 33, 45, 52 and 58
HPV Vaccine Uptake
_/10 girls are unvaccinated
___/10 boys are unvaccinated
HPV Vaccine Uptake 4/10 girls are unvaccinated 6/10 boys are unvaccinated
HPV Vaccination Guidelines
Women
- Routine HPV vaccination is recommended for girls __ and ___ years old.
- Girls as young as age _ years can receive HPV vaccination.
- HPV vaccination is also recommended for teenaged girls ___-___ years old to _____ ___ on missed vaccine or to complete the vaccination series.
- The evidence is ____ at this time to recommend for or against universal vaccination of women __ to___ years old in the general population.
- HPV vaccination is ___currently recommended for women older than age 26.
- Screening for cervical cancer should continue in both ___ and ____ women.
HPV Vaccination Guidelines Women • Routine HPV vaccination is recommended for girls 11 and 12 years old. • Girls as young as age 9 years can receive HPV vaccination. • HPV vaccination is also recommended for teenaged girls 13 to 18 years old to catch up on missed vaccine or to complete the vaccination series. • The evidence is insufficient at this time to recommend for or against universal vaccination of women 19 to 26 years old in the general population. • HPV vaccination is not currently recommended for women older than age 26. • Screening for cervical cancer should continue in both vaccinated and unvaccinated women.
Men • Vaccine approved for boys in ___, but not recommended by ACIP until October 25, ___
. • Boys can begin vaccination as early as age __ years.
• Boys ____- ____ who have not been vaccinated should get “catch-up” shots.
Men • Vaccine approved for boys in 2009, but not recommended by ACIP until October 25, 2011. • Boys can begin vaccination as early as age 9 years. • Boys 13-21 who have not been vaccinated should get “catch-up” shots.
