Rhabdovirus, HIV, and Togaviruses (Rubi, Alpha) Flashcards
1
Q
Rhabdovirus: -Morphology -Transmission -Diagnosis -Treatment -Prevention (disease information is on another card)
A
- neg sense ssRNA, helical nucleocapsid. “bullet-shaped” helical nucleocapsid, enveloped. Rhabdovirus is the family, Lyssavirus is the species, Rabies virus is the important serotype.
- Bite from reservoir (bats, canids, cats, cows, etc) where the virus is present in the saliva 5-7 days before the onset of symptoms. Potentially contact or aerosols too.
- Diagnosis: eosinophil Negri bodies in hippocampal pyramidal and Purkinje cells. Can detect virus directly. Start treatment after dog bite or any contact with a bat.
- Treatment: post-exposure get passive immunization with human rabies Ab + killed vaccine for active immunization (receive vaccine on days 0, 3, 7, 14, 30, 90)
- Prevention: Obligatory vaccine for dogs (live attenuated vaccine).
2
Q
Rhabdovirus
- Pathogenesis
- Disease phases
A
- Viral glycoprotein binds nAChR in post-synaptic motor endplate. Replicates over weeks-months, then symptoms start as it moves along peripheral nerves, motor neurons, and travels to DRG, then to brain.
- Rabies phases:
1. Incubation: 2-16 weeks
2. Prodromal phase: 3-8 weeks. malaise, vomiting, headache, fever
3. Sensory phase: itching, burning pain, sluggishness.
4. Excitation phase: watery eyes, pupil dilation, saliva production, hydrophobia, hallucinations
5. Paralytic phase: paralysis, coma, death
3
Q
Rhabdovirus:
-History of its vaccines
(may not seem important but I could see them asking it, there’s a lot in the lectures about it)
A
- First vaccine made in France, 1885 by Pasteur and Roux. Used infected rabbits nerves that were then weakened by drying them in air for a few days. Method still used in some poor countries.
- 1890 Hőgyes Endre (has a street near Corvin metro named after him) introduced it in Hungary and modified the Pasteur vaccine by diluting it
- Hilary Koprowski adapted the virus to chicken embryo in 1946
- 1967 Human Diploid Cell Culture Vaccine (H.D.C.V.) - inactivated vaccine. Now the most commonly-given form.
4
Q
Retroviruses:
- Morphology
- Components
- Mechanism
A
- positive sense ssRNA that are similar to DNA virus by integrating into host genome
- “env” gene codes for coat proteins and are glycosylated. “gag” gene codes for coating / capsid proteins (the major antigenic proteins). “pol” gene codes for reverse transciptase, integrase, RNase H, and protease
- RNA-dependent RNA polymerase (reverse transcriptase) converts viral RNA into DNA so that it can be integrated into host DNA.
5
Q
What are the retroviruses to be aware of?
A
- HTLV-I: Human T cell Leukemia Virus 1, present in Caribbean and Japan, sexually-transmitted, causes Adult T-Cell Leukemia / Mycosis Fungoides / Sezary syndrome. HTLV-II, found in Native Americans, used to be believed to cause Hairy Cell Leukemia (and sajnos people in our micro department seem to still think this is true). HTLV-I infects CD4+ T cells, HTLV-II infects CD8+.
- Lentivirus: only important one in humans is HIV. HIV used to be called HTLV-III
(Hepatitis B has reverse transcriptase but is NOT a retrovirus because it doesn’t integrate into host chromosome)
6
Q
HIV:
- Morphology
- Proteins and other structural components to be aware of
A
- (+) ssRNA, enveloped. Diploid: 2 molecules of RNA per virion
- DNA polymerase
- RNase H: cleaves RNA as DNA is transcribed so that reverse transciptase can make second complementary strand of DNA
- integrase: integrates viral genome
- protease: cleaves proteins translated from mRNA from gag and pol genes. Target of HAART-2 anti-virals.
- p24: capsid protein, detected for diagnosis
- gp120: surface protein, binds CD4 and CCR5 (macrophages) + CXCR4 (CD4+ T cells)
- gp41: transmembrane protein for viral fusion to host cell
- p17: matrix protein
p7: core nucleocapsid proteins
7
Q
HIV:
- What are the two types of HIV?
- Transmission
- Progression of disease
A
- HIV-1: the more common HIV that causes AIDS. HIV-2: limited to West Africa, less pathogenic than HIV-1
- Transmission: sex, blood, vertical
- Progression:
1. Acute Infection / Prodrome: flu-like, lymphadenopathy, fever. Usually lasts about a week, but can be longer. Viremia w/ drop in CD4+ count, mononucleosis-like symptoms.
2. Latent: immune reaction reduces viral particle number in bloodstream. Lasts up to 10 years (or more) as virus replicates in lymph nodes. Infectious, spread to others in this time. T cell count slowly declines.
3. AIDS stage: begin to have AIDS-defining opportunistic infections and/or their CD4+ count below 200 cells / mm3.
8
Q
HIV:
-Pathogenesis
A
- gp120 binds to both CD4 and a co-receptor (CCR5 for macrophages or CXCR4 for T cells). gp41 then undergoes conformational change to allow it to insert into target membrane -> fusion -> virus enters cytoplasm. People with mutations on CCR5 or CXCR4 have resistance.
- Reverse transcription, implementation into host DNA in dividing T cells but not quiescent ones.
- Remains untranscribed until T cell is activated in response to new infections, at which point there is extensive viral replication and the T cell is lysed.
- Macrophages and dendritic cells harbor the virus in the CNS, so a loss of T cells does not eliminate the virus
9
Q
HIV:
-genes to be aware of
A
- env: codes for envelope proteins (gp41 + gp 120, combined to make gp160)
- gag: codes for capsid proteins like p24 (main antigen of diagnosis) plus
- pol: codes for protease, integrase, and reverse transciptase
- tat: transactivator. regulates synthesis and assembly of infectious viral particles
- nef: protein activates intracellular kinase activity, reduces surface expression of CD4 and MHC molecules on infected cells
- rev: promoter of viral activity, increases gag, pol and env products
10
Q
HIV:
-What are some of the infections and neoplasms that typically occur in HIV/AIDS patients?
A
- Protozoal: Pneumocytosis, Toxoplasmosis
- Fungal: Candidiasis, Cryptococcosis, Coccidiodomycosis, Histoplasmosis
- Bacterial: Mycobacteriosis, Nocardiosis, disseminated Salmonella infections
- Viral: CMV, HSV, VZV, Progressive Multifocal Leukoencephelopathy
- Neoplasia: Kaposi Sarcoma (HHV-8), Diffuse Large B Cell Lymphoma, other B cell non-Hodgkin lymphomas (especially of the brain), neoplasia related to EBV, HPV, and other viruses
11
Q
HIV:
- Diagnosis
- Treatment
A
- Diagnosis: ELISA for antibodies, anti-p24 and anti-env (false-negative if taken too early, so it must be repeated). Confirm with Western blot.
- Therapy:
1. RTase inhibitors: nucleoside and non-nucleoside analogs (NRT and NNRT) e.g. Zidovudin, Navirapine
2. Protease inhibitors, e.g. Saquinavir
3. CCR5 and CXCR4 antagonists
4. Fusion Inhibitors
Usually give triplet combination: NRT + NNRT + Protease inhibitor
12
Q
Leaving this card blank in case I need to add more about HIV later
A
OK
13
Q
Togaviruses - Rubivirus:
- Morphology
- Diagnosis
- Prevention
A
- positive-sense ssRNA, enveloped
- Diagnosis: serology IgM, HI, IF, ELISA, latex-aggl.
- Prevention: MMR live attenuated vaccine
14
Q
Togavirus - Rubivirus:
- Transmission
- Diseases
A
- Respiratory droplets, human host
- Rubella / German Measles: Childhood exanthema, quick rash that lasts 3 days. Postauricular and occipital lymphadenopathy, rash begins on face and spreads down. Infectious 5 days before to 3 days after symptoms. Arthalgia.
- Congenital Rubella: eye defects, deafness, growth retardation, cardiovasc lesions, meningoencephalitis, other congenital malformations.
15
Q
Togavirus - Alphaviridae
- Morphology
- Virus family
- Diseases
- Diagnosis
- Prevention
A
- pos-sense ssRNA, enveloped
- Alphaviruses typically are arboviruses (ARthropod-BOrne) - spread mostly by mosquitoes
- Cause several forms of Equine Encephalitis (Western, Eastern, Venezuelan). Chikungunya (fever, joint pain, rash).
- Diagnosis: cytopathology, IF, RT-PCR, serology
- Prevention: Killed vaccine for EEE and WEE. No treatments.
