MICR 3330 Final Exam Questions And Answers Solved.

sars-cov-2 - correct answers helical nucleocapsid, +ssRNA, linear genome, enveloped what are some features of coronavirus genomes? - correct answers - 5' cap + 3' polyA tail - ORF1a and ORF1b encode two polyproteins - core structural proteins: S, E, M, N what do ORF1a and b encode for in coronaviruses? - correct answers replicase genes, two replicase polyproteins are cleaved into 16 proteins for genome replication and transcription how is ORF1b translated? - correct answers usually translation terminates at ORF1a, ORF1b translation is controlled by a -1 ribosome framshift -1 ribosome frameshift - correct answers changes the reading frame to pass a stop codon proteolytic autoprocessing - correct answers used by ORF1a and b in coronaviruses, protease within the polyprotein cleaves it into functional proteins how are genes downstream of ORF1a/b expressed in coronaviruses? - correct answers via a nested set of subgenomic mRNAs, share the same sequence in their 3' end and all share the same 5' leader sequence mono-cistronic - correct answers each sgRNA can only translate into a single protein why are RNA viruses typically small? - correct answers they lack proofreading abilities in their RdRP nsp14 - correct answers area of ORF1b encoding for an exonuclease domain EXoN - correct answers exonuclease domain encoded in nsp14, confers proofreading activity ACE2 - correct answers angiotensin converting enzyme 2, its receptor is what the spike protein in covid binds to the S gene - correct answers spike protein gene, most important and adaptive as it determines what the coronavirus will bind to long covid - correct answers symptoms due to COVID-19 which persist beyond 12 weeks after the acute phase of infection, patients test negative for SARS-CoV-2 what symptoms are most strongly associated w death from covid-19? - correct answers obesity, diabetes with complications, and anxiety and fear related disorders what is the natural reservoir for COVID-19? - correct answers most likely bats bats - correct answers ancient mammals, experience reduced levels of inflammation, high rates of metabolism, fast HR to generate heat, viral infections occur in the GI tract factors responsible for the fast evolution and genetic diversity of coronaviruses? - correct answers - high mutation rate in RNA viruses - broad host range - frequent recombination - frequent gene acquisition, gene duplication, divergence what two proteases cleave ORF1a/b? - correct answers PL: papain-like protease 3CL: 3C-like cysteine protease spanish flu pandemic - correct answers influenza virus, infected strong individuals, not just the elderly and sick influenza A virus - correct answers FLUAV, most common and severe, responsible for seasonal epidemics, broad host range, many strains and subtypes based on surface glycoproteins HA and NA HA - correct answers hemagglutinin, H1-H18, homotrimer, binds to host cell receptors (sialic acid) for viral entry NA - correct answers neurominidase, N1-N11, homo-tetramer, required for viral egression influenza B virus - correct answers FLUBV, infects humans, milder disease influenza A virus structure - correct answers helical nucleocapsid, -ssRNA genome, linear and segmented genome (8 RNA molecules), enveloped M2 (influenza A) - correct answers forms the ion channels in the viral envelope membrane what is the influenza A nucleocapsid composed of? - correct answers RNA, NP, and the tripartite polymerase (PA, PB1, PB2) ribonucleoprotein complex (RNP) - correct answers what each viral genomic RNA exists as for influenza A, composed of RNA, nucleoprotein, and tripartite polymerase PA (influenza A) - correct answers endonuclease, cleaves capped host pre-mRNA along with 10-13 nucleotides to serve as primer for transcription of viral mRNAS PB1 (influenza A) - correct answers RdRP, synthesizes viral mRNA using snatched oligonucleotides PB2 (influenza A) - correct answers cap-binding, part of the tripartite replicase complex M1 (influenza A) - correct answers forms the matrix later, involved in RNP export our of nucleus and important for virion assembly alternative mRNA splicing (influenza A) - correct answers RNA segment 7 can be alternatively spliced to generate wither M1 or M2, increases coding capacity replication cycle FLUAV - correct answers receptor: sialic acid entry to cytoplasm: endocytosis uncoating: low pH-dependent, depends on M2 function and ion channel translocation of nucleocapsids to nucleus for transcription and genome replication translation: cytoplasm nuclear export: NEP and M1 virion assembly and budding at PM natural reservoir for FLUAV - correct answers waterfowls, all subtypes are found in wild birds with no diseases/symptoms antigenic drift - correct answers minor changes in antigens, evasion of existing immunity antigenic shift - correct answers major shifts in surface antigens, due to re-assortment of genome segments in cells co-infected with different strains H5N1 - correct answers highly pathogenic avian flu H1N1 - correct answers swine flu, RNA segments 1-5 originated from the triple-reassortment strain how are influenza vaccines made? - correct answers prediction of upcoming strains, mass production of vaccine strains using chicken eggs, mammalian cell cultures, recombinant vaccines using baculovirus ion channel blockers - correct answers used for FLUAV, block the ion channel preventing uncoating and infection, amantadine and rimantadine, no longer effective NA inhibitors - correct answers used for FLUAV, relenza and tamiflu, must be used within 36 hours after onset of symptoms why was the spanish flu so fatal? - correct answers originated from a unique and un-identified avian strain tripartite polymerase (FLUAV) - correct answers PA = endonuclease, snatches cap PB1 = RdRP, catalytic subunit PB2 = cap-binding papillomaviridae structure - correct answers icosahedral capsid, dsDNA genome, circular genome with histones, non-enveloped what are the viral strategies of FLUAV? - correct answers - cap-snatching for viral mRNA synthesis - alternative splicing of RNA segments 7&8 - NP binding to viral genome to switch from mRNA synthesis to genome replication what viral strategies are used by human papillomavirus-16? - correct answers - multiple promoters and terminators - alternative splicing of 3 primary transcripts - E7 and E6 push host cell into actively dividing state cottontail rabbit papillomavirus (CRPV) - correct answers first DNA virus known to induce tumors, first mammalian model to study tumorigenesis by a DNA virus HPV transmission - correct answers occurs through direct contact (STD), benign warts depending on the type of virus, certain types cause ano-genital cancers in men and women cervical carcinoma - correct answers cancer of cervix (epithelial), caused by some types of HPV What are the high-risk HPV subtypes? - correct answers 16, 18, 31, 45 (most commonly associated with cervical cancer) what genus are high risk HPV types from? - correct answers most commonly from alpha-papillomavirus genus what are the HPV genera? - correct answers alpha, beta, mu, nu - papillomaviruses, classification is heavily based on nt sequence L1 (HPV) - correct answers major capsid protein, demarcation of genuses is based on the sequence relatedness of this protein HeLa cells - correct answers human epithelial cells of a strain maintained in tissue culture since 1951 and most widely used cell line in research LCR (HPV) - correct answers long control region, origin of replication, binding site of E1 and E2 (transcription enhancers) early promoter and early terminator (HPV) - correct answers express E6+E7 push cell into S phase late promoter and early terminator (HPV) - correct answers express E1, E2, E4, E5 late promoter and late terminator (HPV) - correct answers express L1 and L2 capsid protein/assembly E7 (HPV) - correct answers binds to pRb, degrades it, inducing DNA synthesis and cell cycle E6 (HPV) - correct answers directs ubiquitin-mediated degradation of p53, preventing apoptosis and cell cycle arrest E1 (HPV) - correct answers DNA helicase, binds to Ori; initiates DNA replication E2 (HPV) - correct answers binds to LCR; interacts with E1 to enhance DNA replication and transcription L2 (HPV) - correct answers minor capsid protein, assists in encapsidation of viral genome how does E7 function? - correct answers binds to RB, displacing E2F which is a potent transcriptional activator, pushes the host cell to S phase and uses it to transcribe its own genome how does E6 function? - correct answers complexes with E6AP to bind p53, targeting it for degradation pRb - correct answers retinoblastoma protein, the master brake of the cell cycle machine (tumor suppressor) p53 - correct answers tumor suppressor which activates apoptosis LSIL - correct answers low grade squamous intra-epithelial lesion, basaloid cells replace normal epithelial cells Georgios Papanikolaou - correct answers invented the Pap smear in the 1920s, to observe cervical mucosal cells for abnormality gardisil - correct answers quadrivalent HPV vaccine, targets HPV 6, 11, 16, 18, produced using recombinant DNA in yeast ceravarix - correct answers bivalent HPV vaccine, targets HPV 16,18, produced sing baculovirus and insect cell culture HPV virion structure - correct answers built with 72 capsomers each a pentamer of the major capsid protein L1 how are papillomaviridae different from polyomaviridae? - correct answers only transcribe one strand of dsDNA how do E1 and E2 work to initiate viral DNA replication (HPV)? - correct answers E1 has ATPase and helicase activity, E2 binds DNA at adjacent site and enhances E1 affinity for Ori by bending DNA, E1 forms a hexamer herpesviridae structure - correct answers large, enveloped virion, icosahedral nucelocapsid containing a dsDNA linear genome alphaherpesvirinae - correct answers herpesviridae subfamily which establishes latency in sensory neurons (members = HSV1/2, varicellovirus) betaherpesvirinae - correct answers herpesviridae subfamily which establishes latency in secretory glands and lymphocytes (member = cytomegalovirus) gammaherpesvirinae - correct answers herpesviridae subfamily that establishes latency in lymphocytes (member = epstein-barr virus) herpesvirus evolution - correct answers subfamilies arose 180-220 million years ago, co-evolved and co-speciated with their natural hosts diseases caused by herpesviruses - correct answers oral herpes, chickenpox, shingles, mononucleosis, kaposi's sarcoma, burkitt's lymphoma human cytomegalovirus - correct answers betaherpesvirinae member, infection of newborn babies often leads to death, congenital disease resulting from intrauterine transmission Epstein-Barr virus (EBV) - correct answers gammaherpesvirinae member, discovered by Dr.Epstein and Yvonna Barr in children with lymphoma, primary infection is infectious mononucleosis, linked to Burkitt's lymphoma Varicella-Zoster Virus (VZV) - correct answers causes chickenpox and shingles, member of the alphaherpesvirinae varicella - correct answers chicken pox, from primary VZV infection causes a pruritic vesicular rash zoster - correct answers Shingles; reactivation of a latent viral infection of the dorsal root ganglia (neurons) with VZV Thomas Weller - correct answers grew VZV in cell culture, revealing varicella and zoster have identical CPE, virion morphology and antigenic characteristics (1953) Takahashi - correct answers produced attenuated live vaccine for use in children against varicella (1974) tissue tropism VZV - correct answers mucous membrane, T cells, skin epithelia, sensory neurons (replication initiates in epithelial cells; viremia through infected tonsillar T cells; establishes latency in peripheral neurons) thoracic dermatomal shingles - correct answers involving one of the thoracic dermatomes facial shingles - correct answers occurs if VZV establishes latency in cranial nerves varicella vaccine - correct answers attenuated strain; passage in guinea pig fibroblasts followed by human fibroblast passage acylovir - correct answers nucleoside analog drug for VZV, given at early stage of infection, shortens duration and reduces risk of severe neuralgia and blindness OriS/OriL - correct answers origins of replication for HSV, begin encoding 84 genes on both strands LAT - correct answers latency associated transcripts, transcripts expressed during HSV latency what HSV receptors are involved in entry? - correct answers gB and gC - bind heparan sulfate proteoglycans gD - binds to nectin 1 or HVEM (herpes virus entry mediator) how does transcription occur in HSV? - correct answers viral genes are sequentially expressed, transcription occurs via host RNA pol II immediate early genes (HSV) - correct answers expressed in the first few hours post infection, required for early gene expression and modulating host defense response early genes (HSV) - correct answers expressed 4-8 hours post infection, required for DNA replication late genes (HSV) - correct answers expressed after the onset of DNA replication, required for virion assembly and tegument proteins ICP - correct answers infected cell protein what late genes are required for viral infection? - correct answers two tegument protein, Vhs and VP16 Vhs (HSV) - correct answers virion protein for host shut-off, associates with the cap-binding complex and cleaves mRNAs VP16 - correct answers trans-inducing factor, forms a complex with transcription factors which binds to response elements upstream of the promoters of IE genes, activating their expression what are the functions of tegument proteins? - correct answers activate expression of viral IE genes, degrade cellular mRNAs ICP47 (HSV) - correct answers IE protein which blocks antigen presentation by MHC class I molecules ICP34.5 (HSV) - correct answers reverses effect of activated PKR by dephosphorylating eIF2a, ensuring viral protein translation ICP27 (HSV) - correct answers blocks splicing of pre-mRNAs and shuttles viral mRNA into cytoplasm ICP0 (HSV) - correct answers induces histone acetylation, activating transcription bi-directional replication (HSV) - correct answers how replication initially proceeds, forms replication forks at either Ori, forms two circular genomes rolling circle replication (HSV) - correct answers produces long concatemers of viral genomic DNA, DNA is dragged into capsid and cut (linear) retrograde transport (HSV) - correct answers how HSV infects nerves, virus infects skin or mucosal epithelial cells, followed by this along axons to the cell bodies of sensory neurons Complex Retroviruses (HIV) - correct answers encode Gag, Pro, Pol, Env, plus a set of accessory proteins, contain the genus Lentivirus which includes viruses HIV-1 and HIV-2 HIV structure - correct answers spherical nucleocapsid, +ssRNA genome, linear and diploid genome, enveloped virus what viral strategies does HIV use? - correct answers - ribosomal frameshifting - alternative splicing - reverse transcription - accessory proteins SU (HIV) - correct answers surface protein, attaches to receptor CD4, macrophages, DCs, binding exposes fusion peptide TM (HIV) - correct answers transmembrane protein, initiates fusion with plasma membrane of CD4+ cells CCR5 coreceptor - correct answers R5 or macrophage tropic co-receptor CxCR4 coreceptor - correct answers X4 or T cell tropic co-receptor IN (HIV) - correct answers integrase, inserts proviral DNA into cell genome when does reverse transcription occur (HIV)? - correct answers occurs immediately after capsids enter the cytoplasm of host cells what are the three activities of RTase? - correct answers RdDP (DNA from RNA), DpDP (produced second strand of DNA from cDNA), RNase H activities (degrades RNA) Host DNA-dependent RNA polymerase - correct answers conducts transcription and genome replication of host DNA containing the proviral DNA in the nucleus what is the main receptor for HIV? - correct answers CD4+, tropism for Th cells What are the coreceptors for HIV? - correct answers CXCR4 and CCR5 PBS - correct answers primer binding site LTR - correct answers long terminal repeats, regions of several hundred base pairs of DNA found at both end of the provirus of a retrovirus, contains strong promoters for transcription of full-length viral RNA RT (HIV) - correct answers reverse transcriptase, used to produce DNA from the initial virion RNA genome 9kb (full length) transcript - correct answers encodes Gag and Pol, uses -1 ribosomal frameshifting form fusion Gag-Pol by passing stop codon Rev (HIV) - correct answers accessory protein, regulator of expression of viral proteins, allows nuclear export and translation of the full length and partially spliced mRNAs Tat (HIV) - correct answers transactivator of transcription, transcriptional enhancer How does Rev work? - correct answers unspliced (9kb) and partially spliced (4kb) viral RNAs contain Rev-responsive elements which Rev binds and recruits Exportin 1 and Ran GTP to mediate export how does Tat work? - correct answers recruits kinases and cyclin T1 to phosphorylate C-terminal domain of RNA pol II - enhancing promoter clearance and elongation of transcription RRE (HIV) - correct answers rev-responsive element Vpu (HIV) - correct answers virion protein, unique to HIV, causes CD4 degradation in proteasome enabling formation of progeny virions and release from infected cells acute HIV infection - correct answers 0-12 weeks, fever, malaise, lethargy, nausea Clinical latency of HIV - correct answers 1-7 years, no/mild symptoms AIDS (acquired immune deficiency syndrome) - correct answers dysfunctional immune system phase; infections by many opportunistic pathogens (200 Th cells/uL blood) Rapid HIV progressors - correct answers 10-15% infected, develop late stage (AIDS) symptoms within 3 years Slow HIV progressors - correct answers 70-80% of individuals, develop late stage symptoms 8-10 years after infection Long-term non-progressors of HIV - correct answers 5% of infected individuals; no decline in CD4+ T cell counts; no onset of AIDS genetic factors for non-progressors - correct answers small percentage of the population have a mutation in the gene encoding for coreceptor CCR5 AIDS opportunistic infections - correct answers pneumocystis carinii, candida, mycobacterium tuberculosis, VZV, CMV, Kaposi's sarcoma, lymphoma kaposi's sarcoma - correct answers form of skin cancer frequently seen in acquired immunodeficiency syndrome (AIDS) patients why are there no HIV vaccines? - correct answers - attacking center of the immune system - virus mutates rapidly and constantly - recombination HAART - correct answers highly active antiretroviral therapy (for AIDS), 2 drugs against RTase and 1 drug targeting protease Azidothymidine (AZT) - correct answers nucleoside analogue, selective RTase blocker by having a higher rate of incorporation by RTase than host polymerases, leading to premature termination of reverse transcription Nevirapine (Viramune) - correct answers non-nucleoside reverse transcriptase inhibitor, binds near the active site of RTase Ritonavir (Norvir, RTV) - correct answers a protease inhibitor, targets viral protease viruses which cause respiratory infections + generalized infections beginning in the respiratory tract - correct answers - adenoviruses - rhinoviruses - coronaviruses - FLUAV/FLUBV - measeles - VZV localized infection - correct answers infection is restricted to only one part of the body; do no disseminate to other location (papillomaviruses) systemic infection - correct answers causes infections in organs beyond initial infection site, occurs via bloodstream or the nervous system (PNS to CNS) acute infections - correct answers an infection that results in rapid production of virions, followed by complete elimination of the virus by the host immune system persistent (chronic) infections - correct answers infections that are not resolved by the host immune system; viral genomes or virions continue to be produced at extremely low levels but for long periods of time transforming infections - correct answers oncolytic viruses (simple retroviruses; some DNA viruses; HCV) can induce tumorigenesis and cancer latent/re-activating infections - correct answers after an initial acute infection, virus goes 'dormant', but can be reactivated late on life upon stimulation (herpesvirus)