General Virology Shape of Viruses Spherical Rod-shaped Brick-shaped Tadpole-shaped Bullet-shaped Filament Shapes of Viruses:Spherical Shapes of Viruses :Rod-shaped Shapes of Viruses :Brick-shaped . Tadpole-shaped Shapes of Viruses :Bullet-shaped Shapes of Viruses :Filament Definition of Virus Viruses may be defined as acellular organisms whose genomes consist of nucleic acid, and which obligately replicate inside host cells using the host cell metabolic machinery and ribosomes to form a pool of components which assemble into particles called VIRIONS, which serve to protect the genome and to transfer it to other cells Viral Properties Viruses are obligate intracellular parasites Viruses cannot make energy or proteins independent of a host cell Viral genome are RNA or DNA but not both. Viruses have a naked capsid or envelope with attached proteins Viruses do not have the genetic capability to multiply by division. Consequences of Viral Properties Viruses are not living Viruses must be able to use host cell processes to produce their components (viral messenger RNA, protein, and identical copies of the genome) Viruses must encode any required processes not provided by the cell Viral components must self-assemble Structure of Viruses Virion the complete infectious unit of virus particle Structurally mature, extracellular virus particles. Virion envelope Capsid Viral core Genome The genome of a virus can be either DNA or RNA DNA-double stranded (ds): linear or circular Single stranded (ss) : linear or circular RNA- ss: segmented or non-segmented ss: polarity+(sense) or polarity –(non-sense) ds: linear (only reovirus family) Viral Capsid The protein shell, or coat, that encloses the nucleic acid genome. Capsomer: subunit of capsid (one or several proteins) Functions -Protect the viral nucleic acid -Participate in the viral infection (i.e. mediate attachment to specific receptors on host cell) -Share the antigenicity Nucleocapsid The core of a virus particle consisting of the genome plus a complex of proteins. complex of proteins = Structural proteins +Non- Structural proteins (Enzymes and nucleic acid binding proteins) Symmetry of Nucleocapsid Helical Cubic /Icosahedral/Spherical Complex Helical symmetry Capsomers are arranged in a hollow coil Viruses with helical symmetry possess envelope Influenza Virus (Flu Virus) Measles Virus Mumps Virus Parainfluenza Virus Rabies Virus Respiratory Syncytial Virus(RSV) Cubic or icosahedral symmetry 20 triangles Icosahedral Adeno-associated Virus (AAV) Herpes Simplex Virus 1 (HHV1) Adenovirus B19 Coxsackievirus - A Coxsackievirus - B Cytomegalovirus (CMV) Eastern Equine Encephalitis Virus (EEEV) Echovirus Epstein-Barr Virus (EBV) Hepatitis A Virus (HAV) Hepatitis B Virus (HBV) Hepatitis C Virus (HCV) Hepatitis Delta Virus (HDV) Hepatitis E Virus (HEV) Herpes Simplex Virus 2 (HHV2) Human Immunodeficiency Virus (HIV) Human T-lymphotrophic Virus (HTLV) Norwalk Virus Papilloma Virus (HPV) Polio virus Rhinovirus Rubella Virus Saint Louis Encephalitis Virus Varicella-Zoster Virus (HHV3) Western Equine Encephalitis Virus (WEEV) Yellow Fever Virus Complex Virus Structures A well known example is the tailed bacteriophages such as T4. The head of these viruses is cubic with a triangulation number of 7. This is attached by a collar to a contractile tail with helical symmetry. Viral proteins Surface proteins mediate attachment to host cell receptors Targets of antibody (good antigens, induce protective immune response) Some internal proteins are DNA or RNA polymerases Matrix proteins mediate the interaction between nucleocapsid proteins and the envelope proteins Envelope A lipid-containing membrane that surrounds some viral particles. It is acquired during viral maturation by a budding process through a cellular membrane Properties of enveloped viruses Labile in dry , arid environment Damaged by drying, acid, detergent, and heat Pick up new cell membrane during multiplication Insert new virus-specific proteins after assembly Virus is released by budding Consequences of Properties for enveloped viruses Must stay moist Must not infect the GI tract for survival Must be transmitted in the protective droplets, secretions, blood and body fluids Must reinfect another host cell to sustain Humoral and cell-mediated immunity are needed to control the infection Enveloped California Encephalitis Virus Coronavirus Cytomegalovirus (CMV) Eastern Equine Encephalitis Virus (EEEV) Epstein-Barr Virus (EBV) Hantavirus Hepatitis B Virus (HBV) Hepatitis C Virus (HCV) Hepatitis Delta Virus (HDV) Herpes Simplex Virus 1 (HHV1) Rotavirus Rubella Virus Saint Louis Encephalitis Virus Smallpox Virus (Variola) Vaccinia Virus Herpes Simplex Virus 2 (HHV2) Human Immunodeficiency Virus (HIV) Human T-lymphotrophic Virus (HTLV) Influenza Virus (Flu Virus) Molluscum contagiosum Papilloma Virus (HPV) Polio virus Rhinovirus Varicella-Zoster Virus (HHV3) Venezuelan Equine Encephal. Vir. (VEEV) Western Equine Encephalitis Virus (WEEV) Yellow Fever Virus Properties of naked viruses Stable in hostile environment Not damaged by drying, acid, detergent, and heat Released by lysis of host cells Can sustain in dry environment Can infect the GI tract and survive the acid and bile Can spread easily via hands, dust, fomites, etc Can stay dry and still retain infectivity Neutralizing mucosal and systemic antibodies are needed to control the establishment of infection Naked viruses (non enveloped ) Adenovirus B19 Coxsackievirus - A Coxsackievirus - B Echovirus Hepatitis A Virus (HAV) Hepatitis E Virus (HEV) Norwalk Virus CLASSIFICATION OF VIRUSES Virion morphology Physicochemical properties of the virion Virus genome properties Virus protein proteries Genome organization and replication Antigenic properties Biologic properties RNA-containing Viruses Picornaviruses Retroviruses Astroviruses Bunyaviruses Caliciviruses Othomyxoviruses Reoviruses Paramyxoviruses: Arboviruses Rhabdoviruses:rabies virus Togaviruses Filoviruses Flaviviruses Other viruses Arenaviruses Viroids Coronaviruses: SARS Viral Pathogenesis Viral pathogenesis is the process by which a viral infection leads to disease. The majority of viral infections are subclinical. It is not in the interest of the virus to severely harm or kill the host. The consequences of viral infections depend on the interplay between a number of viral and host factors. Viral Entry Skin - Most viruses which infect via the skin require a breach in the physical integrity of this effective barrier, e.g. cuts or abrasions. Many viruses employ vectors, e.g. ticks, mosquitos or vampire bats to breach the barrier. Conjunctiva and other mucous membranes - rather exposed site and relatively unprotected Respiratory tract - In contrast to skin, the respiratory tract and all other mucosal surfaces possess sophisticated immune defense mechanisms, as well as non-specific inhibitory mechanisms (ciliated epithelium, mucus secretion, lower temperature) which viruses must overcome. Gastrointestinal tract - a hostile environment; gastric acid, bile salts, etc. Viruses that spread by the GI tract must be adapted to this hostile environment. Genitourinary tract - less frequently Outcome of Viral Infection Acute Infection Recovery with no residue effects Recovery with residue effects e.g. acute viral encephalitis leading to neurological sequelae. Death Proceed to chronic infection Chronic Infection Silent subclinical infection for life e.g. CMV, EBV A long silent period before disease e.g. HIV, SSPE, PML Reactivation to cause acute disease e.g. herpes and shingles. Chronic disease with relapses and excerbations e.g. HBV, HCV. Cancers e.g. EBV, HTLV-1, HPV, HBV, HCV, HHV-8 Virus shedding Frequently at the portal of entry Skin, mucous membranes: HSV, HPV Resp. tract: aerosol (influenzav.) Intestinal tract: faeces (Rotav.) Genital secretions: HIV, HBV, CMV Milk: HTLV-I, (HIV), encephalitis viruses Blood: HIV, HBV, HCV, CMV, HTLV-I Viral Clearance or Persistence The majority of viral infections are cleared but certain viruses may cause persistent infections. There are 2 types of chronic persistent infections. True Latency - the virus remains completely latent following primary infection e.g. HSV, VZV. Its genome may be integrated into the cellular genome or exists as episomes. Persistence - the virus replicates continuously in the body at a very low level e.g. HIV, HBV, CMV, EBV. Mechanisms of persistence Limited cytopathic effect Persistence in non-dividing cells (HSV) Constant replication of the viral genome (HPV) Integration of the viral genome into host genome (HIV) Evading the immune response EBV latency in B lymphocytes (EBNA-1) Persistence in special sites (CMV, HPV) Immunosuppression (HIV) MHC-I és MHC-II inhibition (adenov. , HIV) Prions Protein only No DNA or RNA Encoded by cellular gene Alpha helix changes to beta-bleated sheet No antibody response They are inactivated by hypochlorite, NaOH and autoclaving
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