Introduction to Medical Virology PDF

Introduction to Medical Virology Dr. Özge YILMAZLI What is a virus?  means poison in Latin  is not a cellular microorganism  Is NOT alive or dead  can be infective or inactive Acellular organisms (some proteins) General Information Their genomes consist of a single type of nucleic a...

Introduction to Medical Virology Dr. Özge YILMAZLI What is a virus?  means poison in Latin  is not a cellular microorganism  Is NOT alive or dead  can be infective or inactive Acellular organisms (some proteins) General Information Their genomes consist of a single type of nucleic acid (DNA or RNA) It must live in a host cell Because they have NOT got their own metabolisms They depend on the host’s metabolism Reproduction occurs by replication General Information  Obligate intracellular parasite → completely dependent on cellular metabolism and energy  No cellular organelles  “inert” outside the living cell→ does not show metabolic activity outside the living cells Virus-Host Relations      Viruses show a high degree of host specificity. Factors affecting host diversity: Can the virus enter the host cell? Is there a suitable metabolic structure for virus replication after insert the cell? Even if the virus replicates, does it leave the cell and cause the infection to spread? Virus-Host Relationship  The receptor in the host cell: the protein that which the virus will attach  Limited host diversity: virus can infect only related species Wide host diversity: virus can infect a wide range of species   The tropism of virus: the type of tissue or cell that the virus can infect in a host The smallest infectious agent that can only seen with an electron microscope What is a Virion?  A complete (whole) infectious virus particle is called as a "VIRION".  Virion is the extracellular state of the virus.  Its main function is to transport the genome into the host cell and thereby enable its expression (transcription and translation). The simplest virus consists of 2 basic structures: Nucleic acid and protein coat (capsid). Nucleic acid + capsid = nucleocapsid Nucleic acid  It is the active infective unit of the virus.  In DNA viruses, the genome is a single molecular structure.  Some RNA viruses may have a segmented genome.  Reovirus: 10-12  Orthomyxovirus (Influenza) 7 (type C) or 8 (type A and B)  Bunyaviridae (Hantaan virus) 3  All viruses except HIV are haploid  DNA viruses except Parvoviridae are double-stranded  RNA viruses except Reovirus are single-stranded Capsid  It is pure protein  Also known as a protein coat  Gives the shape of the virus  Allows naked viruses to attach to the host cell (attachment proteins are here)  Protomers – capsomeres - capsid It provides the shape of the virus Protects the viral genome from nucleases The Function of the Capsid It allows the virion to attach to the cell by recognizing special receptors. Determines the host diversity of the virus It is the antigenic determinant of the virion Makes up most of the virus mass The Symmetry of the Capsid  Three different virus nucleocapsid shapes have been defined according to the geometrical arrangement of capsomeres:  Icosahedral symmetry  Helical symmetry  Complex symmetry Icosahedral symmetry  = cubic symmetry  Icosahedron (polyhedron) structure  20 triangular surfaces  12 corners Icosahedral symmetry  All faces of the icosahedron are the same  The size of the icosahedron is proportional to the capsomeres size and number  Capsomeres at 12 corners are neighboors to 5 capsomeres and they are called pentons or pentamers  Other capsomeres of the icosahedron are neighboors to 6 capsomeres and they are called hexons or hexamers  It has always 12 pentons, but the number of hexons depends on the virus size. Helical symmetry A simple structure: spiral  viral capsids in a "linear" structure  They are formed by the helical arrangement of the same protein subunits  Their genomes are RNA  Viruses with helical symmetry cause disease in humans are definitely ENVELOPED!  The length of the nucleic acid determines the length of the nucleocapsid  Complex symmetry  Large viruses with a diameter of 200-300 nm  Brick shaped  The nature of symmetry is not fully understood  Poxviruses; humans & animals  Bacteriophages What is envelope? Some viruses are covered with an additional structure called an envelope. These viruses are called ENVELOPED VIRUSES. What is envelope?  The envelope originates from modified host cell membranes.  Enveloped viruses take their envelope from the lipid membrane during their budding from the host cell. The structure of the envelope- consists of 2 basic structures 1. Lipid Layer; Forms the envelope’s main structure; From the nuclear membrane of the host cell in Herpesviridae, From golgi apparatus in Poxviridae, Coronaviridae and Bunyaviridae, from ER in Filaviviridae Others it originates from the cytoplasmic membrane 2. Spiny glycoproteins (peplomers); Extend outward from the lipid layer This proteins are encoded by the virus, synthesized in the host ribosome, glycosylated in the Golgi apparatus and inserted into the host membrane, where the virus will bud Provides specific receptor binding HIV: gp120 and gp41 Influenza: NA and HA Rabies: gp G Enveloped-Naked Viruses  Enveloped Virüses;  Naked Viruses;  Consist of the genome (DNA or RNA), capsid, envelope and viral proteins  Consist of genom and capsid  Resistant to environmental conditions (acid, heating and detergent)  Can spread easily (objects, hands or dust particles)  Not resistant to environmental conditions (acid, heating and detergent)  Must remain wet for spread  It doesn't need to kill the host cell to spread.  Cannot survive in the gastrointestinal tract generally   kill host cell to spread Can live in the gastrointestinal tract Baltimore Classification  Class I  ds DNA viruses  Class II  ss DNA viruses  Class III  ds RNA viruses  Class IV  ss (+) polarity RNA viruses  Class V  ss (-) polarity RNA virusesı  Class IV  ss (+) polarity RNA viruses (with DNA intermediate)  Class VII  ds DNA viruses (with RNA intermediate) DNA Virüsleri ss (+) sense RNA viruses ss (-) sense RNA viruses All negative-strand RNA viruses are ENVELOPEED and have Helical symmetry! ds-RNA Viruses Viral Replication Cycle Stages of Replication  1. Adhesion and entry into the host cell  Recognizes target cell and adheres without energy  Entry into the cell is energy dependent.  Enveloped viruses are ingested by endocytosis, naked viruses by fusion or endocytosis.  2. Uncoating  The virus which is uncoated, in the acidic endosome, leaves it’s genetic material into the host cell. Stages of Replication      3. Early protein synthesis The genome makes the cell synthesize early proteins and these are used in replication. For this, the synthesis of viral mRNA must be provided first. DNA viruses: Except for poxvirus, replicate in nucleus and they use the cell's DNA-dependent RNA polymerase Poxvirus, on the other hand, carries this enzyme in its structure as it replicates in the cytoplasm.  RNA viruses: Replicate in the cytoplasm Retroviridae and Influenza viruses  Viruses that use their own RNA as mRNA are called (+) polarity RNA viruses (picorna, togo, flavi)  (-) polarity RNA viruses have to synthesize mRNA to the host cell and there is no RNAdRNAp enzyme in the cell and carries it in the virus structure. Stages of Replication  6. Assembly  4. Viral genome synthesis   After the synthesis of replication enzymes, first the template strand and then the main genome are synthesized. Genome and other structures assemble independently of energy  RNA viruses assemble in the  5. Synthesis of late proteins  It is the stage in which viral structure components, called capsid and peplomers are synthesized. cytoplasm  On the other hand, protein building blocks of DNA viruses migrate from the cytoplasm to the nucleus, and their recovery occurs in the nucleus Stages of replication  7. Exit from the Cell  Non-enveloped viruses; leave the cell by disrupting the cytoplasm membrane, thereby the host cell autolyzed  Enveloped viruses; It leaves the cell by budding from various host membranes. They first insert their peplomers into the host membranes.