2024-07-08_Lecture 11_Micro V - Viruses I_Slides.pdf

MICRO-V Viruses-I (Read DLA-Viruses) Dr. Maria E. Ramos-Nino...

MICRO-V Viruses-I (Read DLA-Viruses) Dr. Maria E. Ramos-Nino [email protected] Adapted from Dr. Achut Malur lectures References: Jawetz, Melnick & Adelberg’s Medical Microbiology: 28th Edition Medical Microbiology, 9th Edition: Murray et al. 1  Viral-life-cycle Early enzymes Nucleic acid Protein coats Assembly and release Latent © 2013 Pearson Education, Inc. ; Brock Biology of Microorganisms (13th Edition) Elsevier: Medical Microbiology, 8th Edition: Murray et al. https://www.nursinghero.com/study-guides/microbiology/the-viral-life-cycle  Initial infection (inoculation) is followed by disappearance of all viral particles – eclipse phase.  Viral genome takes over the control of the host cell protein making machinery and directs the production towards viral components. This is known as latent period until new virion particles are assembled and released. SOM.MKII.BPM3.7.1.1.M.MV.25 Virus growth cycle 4 Viral life-cycle SOM.MKII.BPM3.7.1.1.M.MV.25 Virus growth cycle 6  Attachment https://basicmedicalkey.com/6-viruses-basic-concepts/ The interaction between a virus and its target cell begins with attachment of the virus particle to specific receptors on the cell Attachment is a critical step as a determinant of target selection by many viruses Requires viral attachment protein and cellular receptors SOM.MKII.BPM3.7.1.1.M.MV.28 Virus proteins and cell receptors 7  Viral Attachment Proteins (VAP) and Receptors Target cell Helper T-cell Epithelial cell https://basicmedicalkey.com/attachment-and-entry-of-viruses-into-cells/ SOM.MKII.BPM3.7.1.1.M.MV.28 Virus proteins and cell receptors 8 Viral Penetration and uncoating 1.Enveloped Viruses: During penetration, enveloped viruses typically fuse their envelope with the host cell membrane (e.g. Herpesvirus, Paramyxovirus, HIV) or are taken into the cell via endocytosis. 2.Non-enveloped Viruses: Non-enveloped viruses penetrate host cells by various mechanisms, including direct penetration, endocytosis. SOM.MKII.BPM3.7.1.1.M.MV.29 Virus penetration and uncoating 9 Viral Penetration and uncoating 1. Direct penetration Virus attaches to host cell receptors, sinks into cell membrane, and injects its genome through a pore into the cell, e.g. poliovirus 2. Fusion 3. Endocytosis https://basicmedicalkey.com/6-viruses-basic-concepts/ Virus glycoproteins attach to host cell Host cell cytoplasmic membrane wraps receptors, envelope-membrane fusion around virus and brings it inside, the occurs, capsid enters, is uncoated and capsid is uncoated, and the viral virus is released, e.g. HIV genome is released into the host cell, SOM.MKII.BPM3.7.1.1.M.MV.29 Virus penetration and uncoating e.g. Influenza virus 10  Viral Replication Uncoating of the viral genome leads to the first step of viral replication, i.e., expression of mRNA (transcription) Translation of mRNA generates the so called “early proteins” which often include synthesis of viral DNA or RNA polymerase and Most other proteins which play an important role Most in viral replication Viral genome replication leads to complementary strand synthesis and additional templates using nucleic acids https://www.researchgate.net/publication/323856102_G-quadruplexes_and_G- quadruplex_ligands_targets_and_tools_in_antiviral_therapy/figures?lo=1 Late mRNA synthesis generates “late proteins” (structural proteins) which participate in the formation of the viral capsomeres SOM.MKII.BPM3.7.1.1.M.MV.29 Virus penetration and uncoating SOM.MKII.BPM3.7.1.1.M.MV.31 Virus gene expression 11  Viral Replication: Genome One convergent point for all viruses is that they all need to go through mRNA (+ve) strand synthesis to produce proteins.  Positive (+ve) nucleic acid (DNA or RNA) is the gene coding strand (or the actual gene sequence)  Negative (-ve) nucleic acid (DNA or RNA) is the complementary strand to the gene coding mRNA (the template strand) https://xaktly.com/Images/Virology/ViralGenomes/ViralGenomesMaster.png 12 SOM.MKII.BPM3.7.1.1.M.MV.31 Virus gene expression  Positive vs. Negative Strands Translation SOM.MKII.BPM3.7.1.1.M.MV.31 Virus gene expression 13  Viral Replication: Central Dogma of Biology Viral replication is a process of generating new genomes  Special cases require specific viral enzymes:  RNA dependent DNA polymerase (reverse transcriptase)  RNA dependent RNA polymerase (RNA replicase) “Central dogma of molecular biology. “F.Crick (August, 1970). Nature 227 (5258): 561–563. SOM.MKII.BPM3.7.1.1.M.MV.31 Virus gene expression 14 General Elements of Viral mRNA Viral mRNA can be processed with the same range of feature that are found on eukaryotic RNA:  5’-5’ N7-methylguanosine-triphosphate CAP  poly A tail (100-200 adenosine residues) When viruses replicate in the cytoplasm they can either make their own 5’ CAP (A) or possess a 3D RNA structure known as internal ribosomal entry site element (IRES) (B) SOM.MKII.BPM3.7.1.1.M.MV.L31.32 Virus mRNA expression 15  Translation of Viral mRNA Different ways of producing viral proteins:  Transcription of individual mRNA molecules from the genome  Segmented genome where each molecule gives single mRNA  Production of a single long polyprotein that is later cleaved into individual functional peptides  Some viral genomes (genetic code) can be transcribed by “shifting the reading frame” with one or two nucleotides and thus produce different mRNA and proteins. khanacademy.org SOM.MKII.BPM3.7.1.1.M.MV.L31.32 Virus mRNA expression 16 Viral Assembly and Release https://www.sec.gov/Archives/edgar/data/1613490/000119312515109909/d746070ds1.htm Newly formed virion can be released by different means:  Budding causes the viral capsid to grab cellular membrane in a form of an envelope which is laced with viral proteins. It is most observed for enveloped viruses  Cell lyses caused by lytic viruses. It is most observed for non- enveloped viruses 17 SOM.MKII.BPM3.7.1.1.M.MV.29 Virus penetration and uncoating  Bacteriophage: Life Cycle Two possible existing bacteriophages:  Virulent (lytic) phage kills the host following infection  Lysogenic (temperate) phage undergoes lysogeny wherein the phage genome becomes a prophage (provirus) either by integration into the host chromosome or exist as an independent entity but replicating with the rate equal to the host genome multiplication SOM.MKII.BPM3.7.1.1.M.MV.26 Bacteriophage replication 19  Viral Hosts and Tropism Viral tropism is the ability of a virus to infect a particular cell (cellular tropism), tissue (tissue tropism) or host species (host tropism). The tropism is defined by few factors:  the viral glycoproteins (VAP) integrated in the outer coat: either the capsid or the envelope that target receptors are acting as doors on the surface of the host cells (susceptibility)  Presence of transcription factors allowing expression of viral genes  Presence of cell enzyme pathways to produce viral proteins is known as “permissivity” https://www.nature.com/articles/nri2623/figures/1?proof=true1 21 Virus Groups by Transmission Virus Group Mechanism of Examples transmission Enteric Fecal-oral route Enteroviruses, Rotaviruses Respiratory Droplets/aerosol Influenza, Rhinoviruses (colds), Measles Zoonotic Vectors (such as Rabies, Influenza A, arthropods) or Flaviviruses animal to human Sexually Sexual contact Herpes simplex Transmitted virus, HIV, HPV Vertically Maternal-neonatal Rubella, CMV, HIV, transmitted transmission HSV Genetic Prions, Retroviruses Blood-associated Transmission via HIV, HBV,HCV, CMV blood 23  Viral Infection: outcomes https://www.researchgate.net/publication/269040074_Advances_and_prospects_of_using_nanocrystalli ne_ceria_in_cancer_theranostics/figures?lo=1 25 Viral Infection: Patterns 1. Acute: Common cold, SARS 2. Acute with late complications: Measles 3. Latent-recurrent: HSV, VZV 4. Chronic: HBV. HCV 5. Chronic with late disease: HIV 6. Slow: JCV, Prions 26 Medical Microbiology, 8th Edition: Murray et al. Atypical viruses and virus-like agents Defective (satellite) viruses cannot replicate without a helper virus.  E.g. Hepatitis D virus (HDV) is a defective virus that can only infect in the presence of Hepatitis B virus (HBV) (helper virus). HDV utilizes HBV surface antigen (HBsAg) for entry into host cell Viroids are infectious agents that contain RNA with some double stranded regions. https://www.wjgnet.com/1007-9327/full/v25/i32/WJG-25- 4580-g002.htm They are associated with certain plant diseases. Prions are infectious agents that are devoid of any nucleic acids (DNA or RNA). They are composed solely of proteins and are associated with diseases in humans and animals. SOM.MKII.BPM3.7.1.1.M.MV.L31.33 Atypical viruses 28  Prions  Prions are the product of a conformational change in normal cellular prion proteins (PrPC) into an abnormal form (PrPSc), which tends to aggregate and accumulate in the brain  Prions cause diseases known as transmissible spongiform encephalopathies, characterized by neuronal loss.  Prions can be acquired through diet, transfusion, surgical procedures, corneal transplants etc. A. Hereditary-~15% of cases. Prion disease- autosomal dominant mutation of PrP (chrom. 20) B. Spontaneous-85% of cases C. Infection-Rare Normal Prion Disease https://opentextbc.ca/microbiologyopenstax/chapter/viroids-virusoids-and-prions/ SOM.MKII.BPM3.7.1.1.M.MV.L31.34 Prions 29