Lecture 2 Virus Transmission and Replication PDF

CHAPTER 2: VIRUS TRANSMISSION AND REPLICATION YAP WEI BOON, PH.D (ASSOC. PROF.) EMAIL: [email protected] IN THE END OF THE LECTURE, STUDENTS ARE ABLE TO: - DESCRIBE THE MODE OF TRANSMISSION OF VIRUSES. - DESCRIBE HOW VIRUSES REPLICATE INSIDE PERMISSIVE CELLS. LECT...

CHAPTER 2: VIRUS TRANSMISSION AND REPLICATION YAP WEI BOON, PH.D (ASSOC. PROF.) EMAIL: [email protected] IN THE END OF THE LECTURE, STUDENTS ARE ABLE TO: - DESCRIBE THE MODE OF TRANSMISSION OF VIRUSES. - DESCRIBE HOW VIRUSES REPLICATE INSIDE PERMISSIVE CELLS. LECTURE OUTCOMES -  A VIRUS INFECTS ADJACENT OR DISTANT CELLS TO ENSURE THE VIRUS SURVIVAL. TO ACHIEVE THIS, VIRUSES MODIFY THE HOST BEHAVIOURS. Loading… EG: RABIES ANIMALS BECOME AGGRESSIVE AND THIS INCREASES LIKELIHOOD FOR THE ANIMALS TO BITE OTHER VICTIMS. SOME VIRUSES ARE TRANSMITTED DIRECTLY DURING herpes SEX OR KISSING (EBV, HBV, HPV). SOME ARE TRANSMITTED FROM PARENTS TO VIRUS NEWBORNS (VERTICAL TRANSMISSION; HBV, HIV, MEV). TRANSMISSION  TRANSMISSION OF VIRUSES ACROSS REGIONS ANIMAL MIGRATION (AVIAN INFLUENZA VIRUS). HUMAN TRAVEL & BEHAVIOURS (SARS CORONAVIRUS, SARS-CoV-2 (Covid- 19). ANIMAL EXPORT/TRADING (MONKEY POX VIRUS).  VECTOR-BORNE TRANSMISSION TRANSMITTED BETWEEN HOSTS BY ORGANISMS FED ON THEM (VECTORS). EG. DENGUE VIRUS, ZIKA VIRUS, YELLOW FEVER VIRUS, WEST NILE VIRUS Loading… VECTORS: ARTHROPODS (TICKS, INSECTS, MITES). ARBOVIRUSES (ARTHROPOD BORNE VIRUSES). -NOT SCIENTIFIC NAME !  TO SURVIVE, A VIRUS MUST FIND ITSELF… carry most compatible A PERMISSIVE HOST CELL! -receptor spike prote to bird to SUITABLE RECEPTORS FOR VIRUS BINDING. THE HOST CELLS PRODUCE TRANSCRIPTION FACTORS AND ENZYMES SUITABLE FOR VIRUS REPLICATION. HOST DEFENSE AGAINST THE VIRUS IS SUPPRESSED OR THE VIRUS DEVELOPS ABILITY TO OVERCOME THE CELLULAR DEFENSE. compatible vivus infection key = lock + a lockcompatibl virus infection  VIRUS REPLICATION: GENERAL - nakedspike S Penetration to bird capsid Attachment ~ removeresid Uncoating - Assembly remove envelope induce host to release Sacha Release cell - genome surrounding lysis host form accede to secess by Docket to Isteathostssystem host's down translation up virus slowing process) cover Transcription + Translation (protein particle synthesis)+ viral genome replication RNA genome stays in cytoplasm To replicate : - DNA nucleus genome stays - in  ON NAKED VIRUSES, SURFACE PROTEINS ARE ON CAPSIDS CAN BE WITHIN DEPRESSION, ON RIDGES, FIBRES, SPIKES. ON ENVELOPED VIRUSES, SURFACE PROTEINS ARE STAGGERED (ARRANGED) ALONG THE VIRUS LIPID ENVELOPES, THEY ARE NORMALLY GLYCOPROTEINS. INITIALLY, A VIRION BINDS WEAKLY TO ONE OR MORE RECEPTORS ON THE CELL SURFACE. WHEN REMAINS ATTACHED, MORE VIRUS SURFACE PROTEINS BINDS TO MORE CELL SURFACE RECEPTORS, THE BINDING BECOMES FIRM. STEP 1: ATTACHMENT OR ADSORPTION  A VIRION FUSES DIRECTLY WITH THE PLASMA MEMBRANE -form (MEMBRANE FUSION). curve protein mediated pathway - form esicle ENDOCYTOSIS S Zest Virus particle in naked virus CLATHRIN-MEDIATED (ADENOVIRUSES). cytoplasm - fuse with vesicle membrane CAVEOLIN-MEDIATED (SIMIAN VIRUS 40). LOW PH IN ENDOSOME LEADS TO ACID-TRIGGERED ENVELOPE FUSION WITH ENDOSOME. ENTRY OF A NAKED VIRUS, WITHOUT ENVELOPE, THEREFORE EMPLOY ENDOCYTOSIS. STEP 2: VIRUS ENTRY  GENOME REPLICATION: MOST RNA VIRUSES: CYTOPLASM, EXCEPT: INFLUENZA VIRUSES (NUCLEUS) AND RETROVIRUSES (NUCLEUS AND CYTOPLASM). WHY IN THE CYTOPLASM: VIRUS GENOME ENCODES ENZYME NECESSARY FOR VIRUS REPLICATION, THEREFORE HAVE NO REQUIREMENT FOR NUCLEAR ENZYMES. INFLUENZA VIRUSES REQUIRE HOST SPLICING ENZYME IN THE NUCLEUS. RETROVIRUSES REVERSE-TRANSCRIBE RNA INTO DNA (CYTOPLASM) AND THE DNA MOLECULES ENTER THE NUCLEUS DURING MITOSIS (NUCLEAR MEMBRANE IS WEAKENED). STEP 3: GENOME REPLICATION AND VIRAL PROTEIN SYNTHESIS  DNA" * "Nucleus where find is you - Dr. Yap MOST DNA VIRUSES REPLICATE IN THE CELL NUCLEUS EXCEPT POXVIRUSES. VIRUS GENOMES ARE TRANSPORTED BY MICROTUBULES TO THE NUCLEAR MEMBRANE. STEP 3: GENOME Loading… REPLICATION AND VIRAL PROTEIN SYNTHESIS  UNCOATING: COMPLETE OR PARTIAL REMOVAL OF THE VIRUS CAPSID TO RELEASE THE VIRUS GENOME. TRANSCRIPTION: REQUIRES PROMOTERS FOR THE BINDING OF RNA POLYMERASE (RNA POL), ASSISTED BY ENHANCER SEQUENCES FOR THE BINDING OF TRANSCRIPTION FACTORS. DNA VIRUSES USE HOST RNA POLYMERASE II TO TRANSCRIBE VIRAL DNA. RNA VIRUSES ENCODE OWN RNA-DEPENDENT RNA POLYMERASE TO TRANSCRIBE VIRAL RNA INTO MRNA. STEP 3: GENOME REPLICATION AND VIRAL PROTEIN SYNTHESIS  PROTEIN SYNTHESIS/TRANSLATION: MEDIATED BY THE 5’ METHYLATED CAP AND 3’ POLY(A) TAIL. 5’ CAP : BINDING SITE FOR EUKARYOTIC INITIATION FACTORS (EIFS). POST-TRANSLATIONAL MODIFICATIONS (GLYCOSYLATION, ACYLATION, PHOSPHORYLATION). ALTERS PROTEIN CONFORMATION, ACTIVITY, LOCALIZATION AND/OR STABILITY OF PROTEINS STEP 3: GENOME REPLICATION AND VIRAL PROTEIN SYNTHESIS  ASSEMBLY OF VIRIONS COMMENCES WHEN THRESHOLD QUANTITIES OF VIRUS GENOMES AND STRUCTURAL PROTEINS HAVE ACCUMULATED IN INFECTED CELLS. NUCLEOCAPSID AND VIRION ASSEMBLY OF A SSRNA VIRUS INVOLVED COATING OF VIRAL GENOME WITH HELICAL CAPSID. ASSEMBLY OF ICOSAHEDRAL CAPSID BEGINS WITH PROCAPSID FORMATION. PROCAPSID CARRIES A COPY OF VIRUS GENOME AND UNDERGOES CONFORMATIONAL CHANGE (SPHERICAL ICOSAHEDRAL). STEP 4: ASSEMBLY  TO DIFFERENTIATE VIRUS GENOMES FROM CELL GENOMES, PACKAGING SIGNAL SEQUENCE IN VIRUS GENOME IS RECOGNIZED BY VIRUS PACKAGING PROTEIN. PACKAGING PROTEINS ARE NORMALLY POSITIVELY CHARGED. TO OVERCOME REPULSION BETWEEN THE NEGATIVE CHARGES OF PHOSPHATE GROUPS. STEP 5: GENOME PACKAGING  BUDDING THROUGH HOST CELL MEMBRANES. STEPS INVOLVED: VIRUS GLYCOPROTEINS ACCUMULATE AT THE MEMBRANES AND ARE INSERTED INTO THE LIPID BILAYERS. MEMBRANES ARE PINCHED OFF AND VIRIONS ARE RELEASED. IT IS LIKELY FOR SOME VIRUSES TO ATTAIN ENVELOPE MEMBRANES FROM ORGANELLES OTHER THAN NUCLEUS SUCH AS NUCLEAR ENVELOPE (HERPES VIRUSES) AND RETICULUM AND/GOLGI (HEPADNAVIRUSES). STEP 6: BUDDING  VIRIONS ARE ALSO RELEASED WHEN THE HOST CELL BURSTS (LYSES) OR RELEASED CONSTANTLY OVER A PERIOD OF TIME WITHOUT LYSING THE CELL. STEP 6: BUDDING THANK YOU!