{"id":5974,"date":"2020-04-20T09:19:57","date_gmt":"2020-04-20T16:19:57","guid":{"rendered":"https:\/\/www.telemedical.com\/wordpress\/?page_id=5974"},"modified":"2021-06-06T15:48:12","modified_gmt":"2021-06-06T22:48:12","slug":"virus-life-cycle","status":"publish","type":"page","link":"https:\/\/www.telemedical.com\/wordpress\/treatment-of-a-disease\/covid19-sars-coronavirus-2-infection\/covid19-biology-and-epidemiology\/virus-life-cycle\/","title":{"rendered":"Coronavirus Life Cycle and Proteome"},"content":{"rendered":"\n

Transmission via airborne and surface contact. Coughing, spitting, sneezing, kissing, breathing, talking, touching, or singing are all mechanisms of spread.<\/p>\n\n\n\n

Body entry through the Eye\/ lacrimal duct , Naso-Oropharynx , and\/or Small intestine.<\/p>\n\n\n\n

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  1. Viral Spike protein binding to cellular surface receptors. Heparan Sulfate,<\/a> ACE-2<\/a><\/strong> , Neuropilin-1<\/a>\/VEGF-A Receptor and possibly Integrin<\/a>, and CD175.<\/li><\/ol>\n\n\n\n

    2. Viral Fusion at the Plasma Membrane versus Endocytosis and then fusion, and\/or Phagocytosis and then fusion. Endocytosis requires cellular host factors ACTR2, ACTR3, RAB7A, CCZ1B, ARPC3, ARPC4, UVRAG .<\/p>\n\n\n\n

    3. Membrane fusion requires Cleavage of the spike protein by furin into S1 + S2 followed by fusion protein activation via TMPSS2 (on membrane surface or endosomes) or Cathepsin L cleavage of S2 (in late endosomes + lysosomes). Other host factors for spike cleavage and membrane fusion include ATP6AP1, ATP6AP2, ATP6V0B, ATP6V0C, ATP6V0D1, TMEM199, CTSL, ATP6V1A, ATP6V1B2, ATP6V1C1, ATP6V1E1, ATP6V1G1, ATP6V1H, TOR1AIP1.<\/p>\n\n\n\n

    4. Endosomes recycl<\/a>e ACE 2 Receptors to the Plasma membrane while viral RNPs enters the cytoplasm to be Replicated into – strand RNAs or directly transcribed into Viral proteins. Transcription of Orf1a polyprotein yield NSP’s 1-11. NSP’s 3 and 4 induce the formation of Double Membrane Vesicles. <\/strong> Host factors for endosomal recycling include retromer (VPS26A, VPS29, VPS35, SNX27, ), commander (COMMD2, COMMD3, COMMD3-BMI1, COMMD4), P3IK (PIK3C3, WDR81, ACP5)<\/p>\n\n\n\n

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    Justapositioning of the ER membranes in the cisterna is probably mediated by NSPs 3 and 4. Initial Fission of Fusion probably creates Double Membrane Spherules that later evolve into larger double membrane vesicles.<\/figcaption><\/figure>\n\n\n\n

    5a. Cellular<\/a> Translation of viral proteome<\/a>.<\/p>\n\n\n\n

    5b. Cellular transcription and replication<\/a> of viral RNA via the RTC ( Replication Transcription Complex<\/a> ) occurs inside Double Membrane Vesicles and + strands are exported through a NSP 3 protein based intermembrane pore. Required host factors for transcription include SLTM, and SPEN.<\/p>\n\n\n\n

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    \"\"<\/a><\/figcaption><\/figure>\n\n\n\n

    6. Protein synthesis (including ribosomal frameshifting)<\/a> and processing at the rough endoplasmic reticulum except vsgRNA coding for some ORFs and Nucleocapsid protein may be translated elsewhere (ie. cytoplasm)<\/p>\n\n\n\n

    7. Viral protein processing in the ER using host factors DPM3 and ERMP1, ERGIC, Golgi apparatus requiring host factors PPID, and CHST14, and Lysosome.<\/p>\n\n\n\n

    8. Viral assembly and budding into the Endoplasmic Reticulum and ERGIC.<\/p>\n\n\n\n

    9. Virus Release or Egress via the Lysosomal Exocytosis System.<\/a> Host proteins involved include FC0L1 SNARE 23, Kinesins, VAMP7, Synaptogamin iv, and the Lysosomal Calcium export channel (TRPLML1).<\/a><\/p>\n\n\n\n

    \"\"<\/a><\/figure>\n","protected":false},"excerpt":{"rendered":"

    Transmission via airborne and surface contact. Coughing, spitting, sneezing, kissing, breathing, talking, touching, or singing are all mechanisms of spread. Body entry through the Eye\/ lacrimal duct , Naso-Oropharynx , and\/or Small intestine. Viral Spike protein binding to cellular surface receptors. Heparan Sulfate, ACE-2 , Neuropilin-1\/VEGF-A Receptor and possibly Integrin, and CD175. 2. Viral Fusion […]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":5833,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-5974","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/www.telemedical.com\/wordpress\/wp-json\/wp\/v2\/pages\/5974","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.telemedical.com\/wordpress\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.telemedical.com\/wordpress\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.telemedical.com\/wordpress\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.telemedical.com\/wordpress\/wp-json\/wp\/v2\/comments?post=5974"}],"version-history":[{"count":0,"href":"https:\/\/www.telemedical.com\/wordpress\/wp-json\/wp\/v2\/pages\/5974\/revisions"}],"up":[{"embeddable":true,"href":"https:\/\/www.telemedical.com\/wordpress\/wp-json\/wp\/v2\/pages\/5833"}],"wp:attachment":[{"href":"https:\/\/www.telemedical.com\/wordpress\/wp-json\/wp\/v2\/media?parent=5974"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}