DNA Tumor Viruses & Herpesviruses PDF

DNA Tumor Viruses Some DNA animal viruses can induce cancer. Polyomavirus SV40 naked icosahedral virus that causes tumors in small mammals (e.g., hamsters and rats) circular dsDNA (Figure 10.15a) host DNA polymerase used for replication small genome with overlapping genes...

DNA Tumor Viruses Some DNA animal viruses can induce cancer. Polyomavirus SV40 naked icosahedral virus that causes tumors in small mammals (e.g., hamsters and rats) circular dsDNA (Figure 10.15a) host DNA polymerase used for replication small genome with overlapping genes transcription and virion assembly occur in nucleus permissive host: virions released after lysis In nonpermissive hosts, integration into host DNA occurs, resulting in transformation: loss of growth inhibition and become malignant, through expression of SV40 large T antigen, which inhibits retinoblastoma (pRb) and p53 ≈ tumor suppressor proteins. tomake autifckl tamers s nse  Herpesviruses large group of dsDNA viruses that cause diseases (e.g., fever blisters, venereal herpes, chicken pox, shingles, mononucleosis, cancer) An important group causes clinical forms of cancer (e.g., Epstein-Barr ∞ Wikipedia virus and Burkitt’s lymphoma). … cytomegalovirus often asymptomatic but can cause pneumonia, retinitis, gastrointestinal diseases. Herpesviruses are able to remain latent for extended periods of time and then reactivate under stress or weakened immune system  enveloped - coated with a lipid membrane from the host cells (Figure 10.16) After attachment, host cytoplasmic membrane fuses with viral envelope, releasing nucleocapsid into cell. In nucleus, viral DNA uncoated, and ㅇ three classes of mRNA are produced. immediate early: encodes regulatory ^ sucvive ㅇ proteins help viras delayed early: encodes DNA replication … proteins viras then replioctes late: encodes structural proteins veleaeel.l from ^ ∅ Replication occurs by rolling circle mechanisms. nucleocapsids assembled in nucleus envelope added during budding through nuclear membrane Release occurs via endoplasmic reticulum.  Herpesvirus life cycle https://www.researchgate.net/figure/Life-cycle-of-herpes-viruses-1-Herpes-entry-by-attachment-and-penetration-2-Release_fig13_33682737  Epstein-Barr virus Causing infectious mononucleosis, often called “mono” or the “kissing disease”, a cold-like disease. Most people in the United States are infected with EBV by the end of their teen years, although not everyone develops the symptoms of mono. Transformation: complex - perhaps involving many viral genes There is no vaccine to protect against EBV infection. B-lymphocytes in cancer Latency in B cells 「 cuusthercells ( thenz cell) lymphoma carcinomas: epithelial cell tumors, e.g., nasopharyngeal _ carcinoma (NPC) – ^ being studied  Burkitt’s lymphoma A form of non-Hodgkin's lymphoma discovered by British surgeon Denis Burkitt, who first identified this unusual disease in 1956 among children in Africa. In Africa, Burkitt lymphoma is common in young children who also have malaria and Epstein-Barr virus. One mechanism may be that malaria weakens the immune system's response to Epstein-Barr, allowing it to change infected B- ~ cells into cancerous cells. l ink The About 98% of African cases are associated with Epstein-Barr ~ ^ infection.  Cytomegalovirus and organ transplantation Cytomegalovirus (CMV) is a ubiquitous virus and the genome is around 235 kb and ~165 genes. Cytomegalovirus viral syndrome is a frequent complication after transplantation due to serological mismatch between the donor and the recipient (the recipient is CMV seronegative and the donor is seropositive), the immunosuppressive drugs, and additional illness risk factors. 30% of patients undergoing allogeneic transplantation and approximately 5% of those undergoing autologous transplantation develop CMV disease. https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC4496754/ no need for CMV RNAclymerase 」 CMV promoter is a strong and constitutive ~ promoter commonly included in vectors used Arrow indicates Cytomegalovirus in genetic engineering work conducted https://www.physio-pedia.com/Cytomegalovirus_(CMV)_Infection in mammalian cells. https://academic.oup.com/jid/article/181/2/721/825650  Cold Sores (Fever Blisters) herpes simplex virus (HSV). There are two types ^ of herpes simplex virus: HSV-1 and HSV-2. Both _ ∅ virus types can cause lip and mouth sores and genital herpes. Transmitted through direct contacts to a cold sore or body fluids; passed to children from kissing by adults. Will persist in the person but symptom will only develop at certain times, e.g., when the immune system is weakened. Recent studies have linked herpes with r work in progress Alzheimer's disease (caution: a research topic in progress). Further readings: https://advances.sciencemag.org/content/6/19/ eaay8828 https://pubmed.ncbi.nlm.nih.gov/29937276/  10.8 Positive-Strand RNA Viruses Bacteriophage MS2 icosahedral infects E. coli by attaching to pilus possesses a small genome encoding four proteins including one subunit of RNA replicase required for viral RNA replication possesses overlapping genes translated directly upon entry because (+)RNA is equivalent to mRNA only ε) canropilale RNA replicase makes (–)RNA, and more (+)RNA is made with (–) template. controls access of host ribosome to translational start sites on its RNA MS2 bacteriophage coat protein interacts with a stem-loop structure from the phage genome spontaneous assembly, release upon lysis  MS2 RNA tagging technique MS2 experiments require generation of two constructs. One construct encodes the RNA of interest (or a certain region, such as only the 3’ UTR) with MS2 hairpins encoded downstream. When transcribed, the MS2 hairpins will form in the end of the transcript and be recognized by the MS2 binding proteins (BPs). MS2-BPs are expressed from the other construct and generally include a fluorescent protein such as GFP. (b) Following transfection, both constructs are transcribed, and the MS2-BPs are translated. The ectopic transcript of interest is Reference on RNA tagging techniques: https://www.researchgate.net/figure/MS2-RNA-tagging-a-MS2- detected and bound by the fluorescent MS2-BPs. experiments-require-generation-of-two-constructs-One- construct_fig1_328046971 MS2 signal (white arrow), marked mCherry flurecent protein, showing localization of HIV-1 https://www.mdpi.com/2079-7737/1/2/116  Poliovirus small icosahedral virus 5'-terminus of RNA covalently bound to VPg protein that facilitates binding to ribosomes, 3'-terminus has poly(A) tail Translation yields a single long, giant protein (polyprotein) that undergoes self-cleavage (post-translational cleavage) to _ generate ~20 smaller proteins necessary for nucleic acid replication and virus assembly. Replication occurs in cytoplasm. Cell lysis occurs, releasing new ← virions. fhamans relunt s.  Polio disease and vaccine A highly infectious viral disease mainly affecting children under 5 years of age, causing nerve injury leading to paralysis, difficulty breathing and sometimes death. Transmitted through faecal–oral spread Vaccines: – _ Oral poliovirus vaccine (OPV): containing live attenuated (weakened) polioviruses. Inexpensive and easy to use. ~ In rare and sporadic situation, may cause vaccine-associated paralytic poliomyelitis (VAPP). – Inactivated poliovirus vaccine (IPV): multi dose given by shot in the leg or arm; the only ~ vaccine used in US. Expensive and hard to administrate. On Aug 25 2020, the Africa Regional Certification Commission certified the WHO African Region as wild polio-free after four years without a case. https://www.cdc.gov/vaccines/vpd/polio/public/index.html  next lecture talk more in Coronaviruses larger virus that replicates in cytoplasm cause respiratory infections, including SARS, in humans and other animals enveloped with glycoprotein spikes on surfaces (Figure 10.19a) Only part of genome encoding RNA replicase is translated Genomic RNA used as template to produce (–) strands from which mRNA is produced and translated. Virions assembled in Golgi complex. released from cell surface