Semester 2 - Hepatitis Virus and Retroviruses Flashcards
What are hepatitis viruses?
A group of viruses causing infection and inflammation of the liver (hepatotrophic virus). They have diversity of nucleic acid composition, structure, and families of origin
What are the human pathogens of hepatitis viruses?
Hep A - Picornavirus (+ssRNA) Hep B - Hepadnavirus (+dsDNA-RT) Hep C - flavivirus (+ssRNA) Hep D - deltavirus (-ssRNA) Hep E - hepevirus (+ssRNA)
What are some characteristics of Hepatitis A
(+)ssRNA, nonenveloped picornavirus
Protein synthesis followed by proteolytic cleavage
What are the clinical features of Hep A?
Range from mild to severe
Sudden onset of fever, malaise, anorexia, abdominal discomfort
10% patients have recurrent illness for 6-9 months following infection
How is Hep A transmitted?
Contaminated food/water
Associated with travellers
How long is the incubation period of Hep A?
2-3 weeks
How is Hep A treated?
Treatment supportive
Vaccine preventable (inactivated) - combo A/B
Heat food/water to >85 Celsius for more than 1 minute or chlorinate
What are some characteristics of Hepatitis B?
Hepadnavirus
Class VII - dsDNA genome with an RNA intermediate
Encodes a reverse transcriptase enzyme
What are the clinical features of Hep B?
Mild fever, dark urine, nausea, anorexia
Vomiting, diarrhea, jaundice (hyperbilirubinemia)
Chronic infection may lead to cirrhosis and liver cancer
How is Hep B transmitted?
Blood products and bodily fluid
Sexual transmission
How long is the incubation period for Hep B?
Variable (weeks to months)
How is Hep B treated?
Nucleotide analogs, RT inhibitors, IFN
Vaccine-preventable (subunit) - combo vaccine
What are some characteristics of Hep C?
Non-A, non-B hepatitis
Flavivirus family (+ssRNA, envoloped)
Gene expression via single polyprotein translation followed by proteolytic cleavage
What is the leading cause of liver cancer and liver transplantation woldwide?
Hep C
What are the clinical features of Hep C?
Fever, fatigue, nausea, vomiting
Dark urine, grey coloured feces, jaundice
Chronic infection leads to liver pathology (failure, cancer)
How long is the incubation period of Hep C?
2-6 months
How is Hep C transmitted?
Infected blood products
Sexual transmission
How is Hep C treated?
IFN and ribavarin
There is no vaccination against HCV
What are characteristics of Hep D?
Deltavirus, requires HBV to replicate viral genome
(-)ssRNA, enveloped
It is NOT a virus. Satellite virus, virusoid, subviral particle
What is a viroid?
A subviral pathogen in plants (no proteins expressed)
What is a virusoid?
Expresses viral protein (HDV)
What is a satellite virus?
Requires another virus for its own replication
What is the nuclear antigen often associated with?
HBV patients with severe liver disease
What is the life cycle of Hep D?
Only infects cells that are also infected with HBV: coinfection occurs simultaneously, superinfection occurs following a primary infection
Replication occurs in the nucleus? - uses cellular RNA polyperases I, II and III, utilizes HBV polymerase enzymes
What are the clinical features of a Hep D infection?
Associated with increased severity of HBV disease. Treatment/prophylaxis is to treat/prevent HBV infection
What are some characteristics of Hep E?
(+)ssRNA, non-enveloped
Enteric
How is Hep E trasmitted?
Fecal-oral - contaminated water, pork/deer meat) Blood products (rare)
What are the clinical features of a Hep E infection?
Fever, fatigue, nausea, anorexia, abdominal pain, joint pain, jaundice, dark coloured urine
Generally self-limiting
Pregnant women - mortality rate high during 3rd trimester
Risk of fulminant hepatitis
What is the incubation period of Hep E?
3-8 weeks
What is the treatment for Hep E?
Supportive
No vaccine currently approved in North America
What are some nutritional factors regarding liver health?
Alcohol
Medications
What are predisposing conditions regarding liver health?
Obesity
Diabetes
Toxin exposure
What are some characteristics of retroviruses?
Class VI Baltimore ssRNA-RT
Diploid genome
Characteristic Gag, Pol, Env genes
What is a Gag gene?
Structural
What is a Pol gene?
Enzymatic (RT, integrase, protease)
What is an Env gene?
Envelope glycoproteins
What are human pathogens of retroviruses?
Human T cell leukemia virus (HTLV-1) HTLV-2 Human immunodeficiency virus (HIV) (HTLV-3) HIV2 = HTLV-4 HTLV-5 Human endogenous retrovirus (HERV)
Who discovered HIV?
Luc Montangier and Robert Gallo
Patient 0 - 1981
Lentivirus family (Lenti=slow)
Where does HIV infect?
CD4 cells (T-cells, macrophages)
What are the clinical features of an acute HIV infection?
Patients may experience generalized symptoms - fever, myalgia, lymphadenopathy
Generally undiagnosed at this stage
What are the clinical features of a chronic HIV infection?
Immune compromise, decreasing CD4+ count, increasing opportunistic infection
What characterizes AIDS?
WBC count below 200 c/ul blood, AIDS-defning illness (Kaposi’s sarcoma, candidiasis, pneumocystis pneumonia)
How many stages of infection of HIV are there?
4 Organization dependent (WHO, CDC etc)
What is stage 1 of HIV infection?
Persistent generalized lymphadeonopathy
What is stage 2 of HIV infection?
mild clinical symptoms, CD4+ <500c/ul
What is stage 3 of HIV infection?
ARC
Advanced symptoms, CD4+ <350c/ul
What is stage 4 of HIV infection?
AIDS Opportunistic infection (AID-defining illness), CD4+ <200c/ul
What is HIV encephalopathy?
AIDS dementia complex
One of the few diseases associated directly with HIV infection
Infection of macrophages and microglia, release of neurotoxins
What are complications of HIV CNS invasion?
Dementia - loss of normal functioning, require assistance for day to day tasks
Progressive - one of the first signs of progression from HIV to AIDS
What is the treatment for HIV encephalitis?
Antiretroviral therapy slows development/progression of AIDS dementia complex in HIV (+) individuals
How is HIV diagnosed?
Serology 6-12 weeks post-exposure
How is HIV transmitted?
Sexual transmission
mother-to-child transmission (gestation, delivery, or breastmilk)
Needle-sharing, blood transfusion
What is the treatment/prevention of HIV?
HAART therapy
Antiviral therapy includes RT inhibitors, nucleotide analogs, protease inhibitors
Post-exposure prophylaxis - health care workers etc
Pre-exposure prophylactic antivirals emerging (daily)
Prevention and education!!
How is an HIV infection initiated?
Viral ligand gp120
Coreceptor gp41
Cellular receptor CD4 (t-cells, macrophages, DCs)
Cellular co-receptors CXCR4 (Tcells), CCR5 (macrophages)
DC-sign cellular receptor on DCs
What does X4-tropic HIV infect?
T-cells
What does R5-tropic HIV infect?
Macrophages
What is transmigration?
Intraepithelial dendritic cells bind HIV using DC-Sign
HIV is internalized into early endosomes
Dendritic cells that have migrated to lymph nodes transfer HIV to CD4 T cells
What is transcytosis
?? Good question
What factors are associated with virulence?
Mutation
Immune cell attack
Chronicity and mildness of symptoms
Accessibility to treatment, prevention, and education
Are there vaccines for HIV?
No, but in development
What are elite controllers?
long-term non-progressors
Aka patients who are positive for HIV but don’t progress to AIDS
What are ND approaches to antivirals/antimicrobials?
Astragalus, goldenseal, licorice root, garlic
St. John’s Wort (inactivates p24?)
What is nutritional support for HIV patients?
Whole food diet, avoid processed foods and refined carbs
Vit A, B, C, E, K, folic acid, biotin, Mg, Mn, omega 3
What are immune boosting herbs?
Garlic
Ginseng
Echinacea
What are some other alternative therapies to consider with HIV?
Acupuncture
Oxygen therapy
Mind/body therapy
Where is HTLV-1 endemic to?
Carribean, Africa, Southern Japan
Where does HTLV-1 infect?
Spinal cord leading to myelopathy and spreads to peripheral nerves
What is HAM/TSP?
HTLV-associated myelopathy/tropical spastic paraperesis
Acute infection is asymptomatic, symptoms may appear following infection
What are the clinical features of HAM/TSP?
Muscle weakness, loss of sensation, pins and needles
Spastic paraparesis or paraplegia
Other neurological symptoms may be present - loss of hearing, loss of vision, tremor
What are the clinical features of a chronic HAM/TSP infection?
Associated with adult T-cell leukemia
What are some characteristics of HTLV-2?
70% homology to HTLV-1
Associated with HAM/TSP
What are some characteristics of human endogenous retroviruses?
HERVs Make up 8-10% of the human genome Evolutionarily conserved - function? May play a role in anti-retroviral immunity Autoimmune diseases (multiple sclerosis)
