MCM 2-22 RNA Viruses II Flashcards
describe Rotavirus
Reovirus, dsRNA, segmented, naked, icosahedral
influenza
orthomyxovirus, -ssRNA, segmented and enveloped
HIV
retrovirus, +ssRNA, 2 copies, enveloped
Rotavirus symptoms & treatment
Severe gastroenteritis in children - watery diarreah, dehydration, maladsorption
-adults ussualy asymptomatic
winter disease
rehydration is esential
Rotavirus life cycle
- attatchment to enterocyte of GI, gets endocytosed
- acidification causes one layer of capsid to release. Early endosome is site of uncoating.
- particle stays intact, “basket weave”, nucleotides can enter and be acted upon by the viral polymerase to form mRNA (transcription first)
- mRNA’s (+RNA with cap) goes to ribosome to be translated. Early = nonstructural proteins that interact with host (interferon antagionists, factors that shut down host translation). Later proteins made are virion proteins including polymerases.
- viral componenets accumulate and are assembled into premature state in region of cell called “viroplasm”
- immature virion moved to ER where it is fully assembled into mature form.
- Exported from cell from exocytosis or eventual lysis, final maturation occurs via gut lumen enzymes.
Rotavirus life cycle - Complicated - look for where/when RNA made and genome made
transcription (RNA made) first, after uncoating. excreted form basket
RNA is then translated into proteins that act as IFN antagonists and host translation shut off proteins.
- other proteins are capsid proteins
- once enough capsid proteins, surface markers are made along with caps that bind and capture the mrna to be pacakged (Genome). = replication.
influenza virus
All kinds of the influenza virus are segmented enveloped ssRNA (-) viruses
-acute respiratory illness in winter
uncomplicated = upper/lower respiratory tract involvement
complicated = primary pneumonia caused by influenza, secondary bacterial pneumonia
-mixed viral and bacterial pneumonia
-muscle involvement (pain) myostitis, and breakdown (rhabdo)
-comes out of nowehre, don’t feel like you are coming down with anything.
Influenza Life Cycle
- contact and respiratory droplet virions bind to ciliated epithelia (eyes, nost, throat, mouth) and induce endocytosis.
- acid treatment of endosome opens virions hemagluttinin molecule into fusogenic form, causing uncoating of genome segments that have NLS
- Segments enter nucleus, RNA- strands used to produce mRNA’s and duplicate -RNA strands
- mRNA and -RNA are transported outside of nucleus for translation and binding to newly-synthesized ribonucleoprotein respectively. Binding of RNA- to ribonucleoprotein is essential to virion formation.
- virion assembly occurs
- virions lead the cell via budding
7 enzyme is required to release virions from cell membrane
flu treatment and prevention
tamiflu and relenza - target A and B, only work early in infection.
Vaccines - take weeks to work. Can be a live mist or inactivated
FLUAD - an adjuvant given in elderly. The elderly immune system did not get a stron genough response to the vaccine to make it immunogenic. ADd an ajuvent to work better.
what causes changes in flu year to year?
point mutations that accumulate to create new subtypes. But also resortment (segmented) can create new strains.
HIV tropism?
Humans only, attacks 2 main cell types. Virus binds to the CD4 and chemokine receptors on T-cells and macrophages. depletion of these cells leads to chronic immune activation causing eventual immunodeficiency
MAcrophage = CD4 and CCR5
Primary T cell = cd4and CCR5 or CXCR4
Susceptible cells express a receptor and co-receptor
how is HIV latency different from herpes latency?
In HIV, can still see low levels of viral RNA in the bloodstream
years go by, t-cell levels slowly decrease until opportunistic infections arise (al herpes viruses and others)
HIV life cycle
Virus enveloped, interacts with CD4 receptor and co-receptor
- Morphological change induces fusion, capsid makes a basket in the cytoplasm
- Replication occurs first, ribonucleotides enter and RT converts RNA to ds DNA
- DS dna enters nucleus, integrates with host genome
- when RNA pol II transcribes this portion, it will also trasncribe viral RNA to be translated in nucleus and viral genomic RNA (replication)
- The viral particles and genomic RNA come together, assemble, and bud
HIV must enter the nucleus because it does not have RDRP. instead it creates DNA that enters the nucelus which tehn gets transcribed by RNA pol II of the host.
HIV clinical features
HIV is an enveloped ssRNA (+) virus. Acute HIV infection presents flulike symptoms with a rash. After that, there is a long latent period that appears asymptomatic outwardly, but is accompanied by immune changes. This leads to hallmark infection, then a low CD4 count, then AIDS. Symptoms of AIDS include meningitis, retinitis, tuberculosis, skin tumors, and esophagitis.
roadblocks to curing aids
- Not being able to reverse the permanent incorporation of viral DNA into the host genome
- Viral utilization of host RNA pol II to replicate the viral genome; host RNA pol II cannot be targeted by drugs, as it would cause the patient to die
diagnosis of HIV
serological assays for antibodies
nucelic acid assays for viral load
CD5 t-cell count
HIV life cycle
When HIV encounters a CD4 cell, its glycoproteins bind to the CD4 receptors. Binding to a second receptor causes the HIV glycoprotein to change shape. This shape change leads to the release of the hydrophobic fusion portion of the protein, further leading to fusion and release of the capsid into the cytoplasm. This causes the capsid to allow things in and out of it; this is the uncoating phase. Two virion-bound reverse transcriptase enzymes convert the two genomic RNA (+) strands into two circular DNA molecules. (The two genomic RNA strands are both complete copies of the genome; HIV is not a segmented virus.)The DNA usually enters the nucleus when the cell is activated for division (since the nucleus dissolves in prophase, making it easier for it to enter). The DNA molecules then integrate into areas of active transcription. The incorporation is permanent. Host RNA pol II replicates the viral genome from the incorporated DNA. Viral proteins are synthesized from the mRNA in the cytoplasm. These proteins are assembled into virion particles, which leave the cell by budding. Proteases outside the cell finalize the maturation of the virion.
When does HIV usually enter the nucleus?
nucleus when the cell is activated for division (since the nucleus dissolves in prophase, making it easier for it to enter). The DNA molecules then integrate into areas of active transcription
integrase?
viral enzyme bound to the HIV DNA, allows it to recombine into the host cell chromosome. There for life, unable to eradicate.
how and where does RDRP work in rotavirus?
RDRP synthesizes mRNA and dsRNA genome segments in the cytoplasm
influenza vaccines are trivalent because
Two strains of A virus and one strain of B are selected as the most prevalent strains (gamble)
what are the symptoms of influenza infection?
fever, body aches, and extreme fatigue due to interferon response
