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Made microscopes, discovered "wee animalcules" |
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Showed that organisms do not arise by spontaneous generation |
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When viruses were recognized distinct from bacteria |
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Found the agent of tobacco mosaic disease |
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Suggested that the tobacco mosaic virus is a distinct agent, not just small |
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Discovered that the agent of foot and mouth disease is filterable |
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First discovered human virus |
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Developed a set of criteria for positive identification of an infectious agent |
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Progeny infectious virus particles |
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Set of proteins that encase a viral genome so it can invade cells |
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Lack of genetic information |
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Is the reason why viruses cannot produce the apparatus for metabolism or protein synthesis |
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Are assembled to form virus particles |
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Very small (200-400 nucleotides) circular RNA molecules with a rod-like secondary structure. No caspid or envelope, associated with certain plant diseases. |
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Satellite, viroid-like molecules, (1,000 nucleotide size) Dependent on the presence of virus replication for multiplication. Packaged into virus capsids as passengers |
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Infectious agents generally believed to consist of a single type of protein molecule with no nucleic acid component |
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Units commonly used to describe viruses |
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The number of genome types |
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All viruses follow this rule |
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Viral genomes must make mRNA that can be read by host ribosomes |
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(+) Strand/Coding strand is defined as |
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The strand of DNA with equivalent polarity |
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Complement of (+) strand is the |
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mRNA is synthesized in the_______except for poxviruses |
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DNA virus translation of early mRNA is required for |
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DNA pol in DNA virus replication cannot |
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Initiate DNA synthesis, can only extend, require primers |
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Positive (+) strand mRNA can be |
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Negative (-) strand, known as the complement of the (+) strand |
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The unique pathways from various viral genomes to mRNA are used to |
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Define specific virus classes |
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RNA Pol I transcribes what genes? |
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5.8S, 18, and 28S rRNA genes |
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RNA Pol II transcribes what genes? |
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All protein-coding genes, some snRNA genes |
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RNA Pol III transcribes what genes? |
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tRNA genes, 5S rRNA genes, some snRNA genes, genes for other small RNA's |
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Positive (+) Strand is in the |
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Negative (-) strand, or complement strand goes in the |
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Gaps must be filled in gapped, circular dsDNA genomes because: |
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You need a double stranded form of DNA in order to produce mRNA |
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The unusual gapped DNA genome is produced from an RNA template by a viral encoded: |
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Reverse transcriptase enzyme homologous to that encoded by the retroviral genomes |
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What must precede mRNA synthesis in dsDNA? |
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Repair process that fills gaps |
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What is an inherent problem with the ssDNA genome? |
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RNA can only be made from a double-stranded DNA template |
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DNA synthesis must precede mRNA production in what viral genome? |
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RNA virus genomes encode novel |
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RNA dependent RNA polymerases |
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dsRNA cannot be translated by: |
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Single stranded RNA (ssRNA); (+) strand RNA can be ___________ into protein by host ribosomes |
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The dsDNA intermediate integrates into host DNA and becomes a: |
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permanent part of the host genome (a "provirus") |
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Single strand RNA, (-) sense cannot be |
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Definition
Translated directly into protein, must be copied to produce a (+) strand mRNA that can be translated |
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Features that protect the ends of Positive-strand RNA viruses |
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Definition
5' caps, 3' poly(A) tails, 5' attached proteins, RNA secondary structures |
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Features that protect negative-strand, Retro, Ambisense RNA Viruses |
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Terminal sequence complementarity, toleration of sequence variation in the termini, terminal redundancy |
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Population of viruses that are related, but not homogenous |
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The typical genome size of RNA viruses |
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Somatic cells from an experimental animal or taken from a human patient which can be maintained for a short period in culture |
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All cells are connected to each other, no holes in between |
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CPE Variety of morphological changes |
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Intracellular abnormalities for an infected cell that can be seen by light microscopy |
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Ability of red blood cells to attach specifically to virus-infected cells |
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Tissue Cuture Infective Dose in order to kill 50% of inoculated tissue culture cells |
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Dilutions of virus is used to infect a cultured cell monolayer, counting plaques is used to determine titer |
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(# plaques)(reciprocal of dilution)(dilution factor) |
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Multiplicity of Infection (MOI) |
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Average amount of virus per cell used in an infection |
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Observed haemagglutination of red blood cells by influenza virus |
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Calculating Multiplicity of Infection |
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MOI= pfu/cell= (pfu/ml*[#ml])/(#cells) |
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Hemagglutination-Inhibition |
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Used to determine the minimum amount of antibodies to eliminate virus |
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Viral nucleic acid is uncoated |
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No extracellular virus is detected |
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Used to predict the fraction of cells infected with a given number of particles. |
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Functions of the Virion Coat |
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Protects genome, attachment, penetration, initiation of replication cycle, interacts with host immune system |
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Vital for allowing viruses to establish infection |
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Consists of multiple copies of protein molecules, protein shell, and subunits (capsomers) |
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Used to view molecular interactions, < 10 A resolution, virus must form crystals |
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Nuclear Magnetic Resonance (NMR) |
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Used to determine the structure of individual viral proteins in solution |
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Amplitude (Helix definition) |
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Distance covered by each complete turn of the helix |
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Helical, naked animal viruses |
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All_______have an outer lipid envelope |
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Advantage to helical structure |
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Viruses with small genomes can generate protection while not encoding many different capsid proteins, any volume can be encapsidated by varying the length of the helix |
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Description of the triangular face of a large icosahedral structure in terms of its subunits into smaller triangles or facets, number of subunits per face on the icosahedron |
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# of Subunits/capsid must equal |
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60 identical subunits that interact in an identical manner |
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180 identical subunits, similar interactions |
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Too large to diffuse across plasma membrane |
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long lived but not truly indefinite stability; Metastability |
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Not a passive processes, requires use of normal cellular processes. |
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Are required for virus binding to cells |
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Exceptions to the Virus Receptor rule |
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Yeast, Fungi, and Plant Viruses |
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Refers to the type of cells that a virus can infect |
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Is determined by cell receptors, biggest determinant if virus crosses species lines. |
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Interaction between receptor and viral ligand |
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Combination of several receptors with viral ligands |
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Identification and Isolation of Viral Receptors |
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Done using antibodies, observing antibody/receptor interactions |
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Has a large number of regions on target (epitope) that it can bind to. |
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Can only recognize one target site (epitope), specific |
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Molecules that serve as receptors |
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Specific proteins (often glycoproteins), Glycolipids, Glycoaminoglycans |
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Viral Attachment Proteins (Enveloped Viruses) |
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Glycoprotein anchored in the envelope |
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Viral attachment Proteins (Nonenveloped Proteins) |
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Neuraminidase, Haemagglutinin |
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Receptor-mediated Endocytosis Types |
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Cytoplasm -> Coated Pit -> Coated Vesicle -> Acidification |
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Non-enveloped, binds to cell receptor via fiber protein, Protein VI disrupts endosomal membrane, penton base/integrin receptor results in endocytosis |
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N terminus is exposed to VP1 and results in insertion into the cell membrane that allows for introduction of RNA into cytoplasm |
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All DNA viruses (except Poxviruses), Retroviruses (RNA), Influenza (RNA), Borna Disease Virus (RNA) |
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All other RNA viruses other than Retroviruses, Influenza, and Borna Disease virus |
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Has the ability to bind to mucus, enveloped, segmented single-stranded RNA, negative stranded |
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Infects avian species, humans, mammals, has surface glycoproteins (HA and NA) |
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Isolated from humans, but also swine from China, has only one single multifunctional glycoprotein, hemagglutin-esterase-fusion protein (HEF) |
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Important antigens for protective immunity |
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Small, gradual changes that occur through point mutations in the two genes that contain the genetic material to produce the main surface proteins, HA/NA |
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New virus strains that may not be recognized by antibodies to earlier influenza strains, leads to major pandemics/epidemics |
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Major structural protein that interacts with the RNA segments to form RNP, type-specific antigen |
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Binds to sialic acid, penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane, major antigen against neutralizing antibodies |
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Homotrimer of noncovalently linked monomers |
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Prerequisite for the virus to be infectious, determinant in parthenogenesis |
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Integral membrane protein, homotetramer, head domain is enzymatically active, |
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Distal tip of HA molecules |
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Definition
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Sialic acidic linkages alpha 2,3/2,6 |
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Definition
Determinants in restricting the transfer of influenza virus directly from avian species to humans |
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Responsible for cleavage-activation |
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Facilitates the flow of protons from the lumen of the endosome into the virion interior, bringing about dissociation of protein-protein interactions between the HA cytoplasmic tail and M1, M1 and lipid/or RNPs and M1 from the RNPs |
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Antiviral against influenza, blocks early step in replication, acts as a channel blocker for M2 (ion channel) |
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Influenza RNA Replication and mRNA synthesis |
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Cap stealing or snatching |
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Primers are taken from the 5' end of host mRNA's, influenza virus needs this to initiate transcription |
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Cap-dependent endonuclease |
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Removes caps from mRNA, associated with PB2 that is part of RNA pol complex |
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Influenza Initiation Primer |
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Definition
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Hemagglutin-esterase-fusion protein (HEF) |
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Influenza C multifunctional glycoprotein |
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Amino acid sequence variability (HA/NA) in influenza A |
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Definition
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Naked Genome Parthenogenesis |
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Viral Matrix Protein (M1) |
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Underlies the lipid bilayer to associate with the ribonucleoprotein core of the virus, most abundant virion protein |
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HA roles in replication cycle |
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Definition
Binds to sialic acid, penetration into cell cytoplasm, binds to neutralizing antibodies |
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Receptor-Mediated Endocytosis |
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How influenza enters cells, vesicles fuse with endosomes. |
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Antiviral against influenza, channel blocker of M2 ion channel. |
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Facilitates the flow of protons from the lumen of the endosome into the virion. |
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Fungal toxin that blocks mRNA influenza synthesis by inhibiting RNA pol II |
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