Virology Lecture Notes (CLS212) PDF

College of Applied Medical Sciences Clinical Laboratory Sciences department Virology Dr. Hala Aldahshan CLS 212, Lecture-2 2022  History § Thro...

College of Applied Medical Sciences Clinical Laboratory Sciences department Virology Dr. Hala Aldahshan CLS 212, Lecture-2 2022  History § Through the 1800s, many scientists discovered that something smaller than bacteria could cause disease and they called it virion (Latin word-poison) § In the 1930s, after the invention of electron microscopes x-ray crystallography, viruses finally could be seen. § The first photographs of viruses were obtained in 1940.  OBJECTIVES Ø General characteristics of viruses. Ø Structure & symmetry of viruses. Ø Classification of viruses. Ø Steps of virus replication.  Characteristics of viruses 1. Acellular particles 2. Particles composed of Internal core, Protein coat, Some Viruses have lipoprotein membrane called (envelope) 3. Obligate intracellular parasites 4. No ATP generating system 5. No Ribosomes or means of Protein Synthesis Image created by Ben Taylor, Public Domain, Via Wikipedia commons https://open.oregonstate.education/generalmicrobiology/chapter/introduction-to-viruses/  Properties of Micro-organisms Characteristic Parasite Fungi Bacteria Virus Cell Yes Yes Yes No Type of nucleus Eukaryotic Eukaryotic Prokaryotic ----- Nucleic acid Both DNA Both DNA Both DNA DNA or & RNA & RNA & RNA RNA Ribosomes Present Present Present Absent Mitochondria Present Present Absent Absent Replication Mitosis Budding or Binary fission Special mitosis How Big is a Virus?  Size of viruses § Virus particles can only be seen by an electron microscope. § Most viruses range in sizes from 10-300 nanometers. Tortora, G. J., Funke, B. R., & Case, C. L. (2013). Microbiology: An introduction. Page 372 The size of a virus is small relative to the size of most bacterial and eukaryotic cells and their organelles. https://bio.libretexts.org/  Structure of Virus 1. Genome: The nucleic acid material containing the genetic information and its either DNA or RNA. 2. Capsid: A protein structure designed to protect the genome. It is composed of many small protein units called capsomeres. 3. Envelope: A lipid bilayer membrane found in some viruses. It is derived from the host cell membrane or nuclear membrane and never made by the viruses themselves.  Structure of Virus 1-Virual Genome § Viruses have either DNA or RNA § Viral NA are usually circular, but some are linear. § Both DNA or RNA can be Single Strand (ss) or Double Strand (ds) § Viruses have four categories based on that 1. ss DNA viruses 2. ds DNA viruses -most common. 3. ss RNA viruses - most common. 4. ds RNA viruse § Contains several genes that are responsible for the production of non-structural protein (enzymes and regulatory proteins) and structural proteins (proteins incorporated in the structure of the progeny virus)  Diversity of viral genomes Introduction to Viral Structure, Diversity and Biology∗ Boriana Marintcheva, in Harnessing the Power of Viruses, 2018  Structure of Virus 2- Virus Capsid § Capsid is the protein coat inclosing the genome. § Capsid subunits called (capsomeres). § The capsid is designed to give shape, size, and protect the virus nucleic acid from environmental damage and facilitates its entry into the cells. lippincott's microbiology 3rd edition § Capsid and Nucleic Acid are called “neocleo-capsid”.  Capsid Capsids of viruses have different shapes and symmetry. Based on the arrangement of capsomeres they can be: 1. Helical: coiled tubes. 2. Icosahedral: many sided. 3. Bullet shaped. 4. Spherical. 5. Complex: combination of shapes Types of viruses. Helical, polyhedral, spherical and complex structure models. Image Credit: VectorMine / Shutterstock https://ib.bioninja.com.au/standard-level/topic--evolution-and-biodi/553-classification-of-biodiv/virus-classification.html  Structure of Virus 3- Virus Envelope § Lipid containing membrane surrounding the nucleocapsid used in defining a viral family. § The virus that is not enveloped is known as naked virus or nonenveloped virus. § Often there are projecting spikes of glycoprotein which are important as viral attachment protein to host cell or erythrocytes. lippincott's microbiology 3rd edition  Atypical Virus-Like Agents Viroids Naked ssRNA without protein coat or envelop Requires host cell DNA-dependent RNA polymerase to replicate Plant pathogens Prions § Entirely composed of protein § Have no DNA or RNA § Cause fatal neurological disease in animals such as Mad cow disease and Creutzfeldt- Jacob disease (CJD) in human  Viral proteins § The outer viral proteins Mediate attachment to specific receptor Induce neutralizing antibodies Target of antibodies § The internal viral proteins https://viralzone.expasy.org/612 Structural protein ( capsid protein of enveloped virus ) Nonstructural protein ( enzymes) All ssRNA virus (-) polarity have transcriptase (RNA dependent RNA polymerase) inside virions Retro virus & HBV contain reverse transcriptase  Classification of Viruses Viruses are classified by the following characteristics: 1. Type of genetic material (DNA or RNA). 2. Shape of capsid. 3. Number of capsomeres. 4. Size of capsid. 5. Presence or absence of an envelope. 6. Type of host that it infects. 7. Type of disease that it produces. 8. Target cells. 9. Immunologic or antigenic properties.  Replication of Viruses The ability of viruses to infect or invade the target cell and multiply inside it and subsequent escape outside the cell. 1-Recognition 2-Attachment The most important step A. Early phase 3-Penetration 4-Uncoating 5-Biochemical synthesis B. Eclipse Phase (late) 6-Assembly of virus 7-Release  Virus Replication 1) Attachment (adsorption) : Adsorption involves attachment of viral surface proteins or spikes to the cell surface receptor proteins 2) Penetration: The entire virus enters the cells. 3) Un-coating: Release of the viral genome from its protective capsid to enable the viral nucleic acid to replicate. 4) Biosynthesis: This step result in the production of pieces /parts of viruses (e.g. viral DNA and viral proteins) (genome replication and genome expression) 5) Assembly : The viral parts are assembled to create complete virions inside the host cell 6) Release: Escape of the complete virions from the host cell. Naked viruses à Cell lysis (cell death). Enveloped viruses à Budding.  In influenza virus infection, viral glycoproteins attach the virus to a host epithelial cell. As a result, the virus is engulfed. Viral RNA and viral proteins are made and assembled into new virions that are released by budding. https://courses.lumenlearning.com/microbiology/chapter/the-viral-life-cycle/  Adsorption Attachment site: - glycoprotein - folding in the capsid proteins.  Penetration Step A. Fusion Some enveloped viruses fuse directly with the plasma membrane. Thus, the internal components of the virion are immediately delivered to the cytoplasm of the cell. (enveloped viruses)  Penetration Step B. Endocytosis Entry via endosomes at the cell surface. Some viruses are unable to fuse directly with the plasma membrane. These viruses are taken into endosomes. Then internal components of the virus is released into the cytoplasm of the cell. (both enveloped and non-envelope viruses) Penetration Step  Replication Adsorption (Attachment) Penetration Uncoating Release of viral genome - cytoplasm - nucleus  Synthesis of viral components mRNA Viral genome transcription mRNA +ssRNA acts directly Viral proteins mRNA translation viral proteins cell ribosome - enzymes - structural proteins replication of viral genome  Replication Adsorption (attachment) Penetration Un-coating Synthesis of viral components mRNA Viral proteins Nucleic acid Assembly Nucleic acid + viral proteins = Virions Release  Release 1-Budding 2- Cell lysis Enveloped viruses use Nonenveloped viruses budding lyse the host cell viral proteins are placed –viral proteins may into host membrane attack peptidoglycan or nucleocapsid may bind membrane to viral proteins envelope derived from host cell membrane, but may be Golgi, ER, or other virus may use host actin tails to propel through host membrane  Replication Cycle of HIV virus e.g. HIV: enveloped virus.  Replication Cycle of Picornavirus e.g. Picornaviruse: non-enveloped virus  The Outcome of Viral Infections The range of structural and biochemical effects that viruses have on the host cell is extensive. These are called cytopathic effects. Ø Lytic Infection Host cell dies at the end of virus replicative cycle (e.g. influenza & polio) Ø Persistent Infection Host cell remains alive and continues to produce progeny virions. (e.g. Hepatitis B infections)  The Outcome of Viral Infections § Latent Infections Host cell remains alive, and viruses enter a dormant state where it dose not replicate until some trigger causes them to activate and replicate again. (e.g. HIV & Herpes infections). § Transformation Infections Infected host cell is transformed by the virus. (those are viruses that carry oncogenes which my lead to cancer in host cells. They can be DNA or RNA viruses) (e.g. HBV, HCV). 15 to 20 % of all cancers in humans  α-Herpes Virinae Herpes Simplex Virus Type 1: Herpes Simplex Virus Type 2: Fever Blisters Genital Herpes § Both are infection in the skin or mucus membranes of the mouth, lips or genitalia. § Primary infection: a lesion called Blister which is watery and cause itching. § When the blister is healed the virus shed to the nerve to hide from the immune system. § latent infection: Recurrent infection can happen when there is a decrease in the immunity. Transmission: transmitted through close contact with infected person who is shedding virus from the skin. Latency of HSV-1  β-Herpes Virinae It is called CMV because the infected cells are greatly enlarged and multinucleated. Initial infection commonly occurs during childhood. The infection in infants or children is usually asymptomatic; they continue to shed the virus for months in virtually all body fluids (tears, urine, and saliva) without causing detectable damage or clinical illness. The primary infection in immuno-competent persons presents as mononucleosis-like syndrome which soon resolves. Most of them remain asymptomatic for life. After infection, the virus remains latent in the body for the rest of the person's life. Disease rarely occurs unless immunity is suppressed either by drugs, infection (HIV) or old-age, immuno-suppressive drugs. Transmission: occurs from person to person through bodily fluids (e.g. urine, saliva, blood, or breast milk)  γ-Herpes Virinae Epstein-Barr Virus (kissing disease) Cause: infectious mononucleosis Symptoms: fever, sore throat and swollen lymph glands. Sometimes, a swollen spleen or liver involvement may develop. Infectious mononucleosis is almost never fatal. Although symptoms of infectious mononucleosis usually resolve in 1 to 2 months, EBV remains dormant or latent in a few cells in the throat and blood for the rest of the person's life. Periodically, the virus can reactivate and is commonly found in the saliva of infected persons. This reactivation usually occurs without symptoms of illness. Epstein-barr can reoccur at any time especially after illness or stress. Transmission: by intimate contact with saliva that contains the virus.  Influenza virus There are 3 types of inflenza viruses: § Influenzavirus A: causes of all flu pandemics and infect humans, other mammals and birds § Influenzavirus B: infect humans and seals § Influenzavirus C: infect humans and pigs Inflenza A: The most virulent human pathogens among the three influenza types and causes the most severe disease. There are several types of protein from (Hemagglutinin) H1 to H5 and (Neuraminidase) N1 to N5 giving several kind of infections that transmit between animals and human, such as bird flu, swine flu and many others.  Corona Virus Enveloped positive strand RNA virus Coronaviruses are named for the crown-like spikes on their surface Human CoVs isolated in the 1960s Emerging Coronaviruses: A human corona viruses typically cause common colds. It is estimate that coronaviruses cause 15-30% of all colds. SARS-CoV-1-and MERS Ab in human is not common, showing that they have not circulated widely in humans. Covid-19 is the third major outbreak of coronaviruses in the last 20 Years, but the first in the 21 century to become a pandemic. It affect all the glob except Antarctica. Emerging Coronaviruses: Docea AO, Tsatsakis A, Albulescu D, Cristea O, Zlatian O, Vinceti M, Moschos SA, Tsoukalas D, Goumenou M, Drakoulis N, Drakoulis N, et al: A new threat from an old enemy: Re-emergence of coronavirus (Review). Int J Mol Med 45: 1631-1643, 2020  Middle East Respiratory Syndrome Coronavirus (MERS-CoV) § First identified in Saudi Arabia (September 2012) § Different from any other corona virus previously found in people § Spread from an infected person to others through: 1. The air by coughing and sneezing 2. Close personal contact, such as touching or shaking hands.  Symptoms & Complications Most people confirmed to have MERS-CoV infection have had severe acute respiratory illness with: § Fever § Cough § Shortness of breath § Some people also had gastrointestinal symptoms including diarrhea and nausea/vomiting. § Complications, such as pneumonia and kidney failure § Incubation period for MERS 2-14 days § People with pre-existing medical conditions, more likely to become infected with MERS, or have a severe case § Pre-existing conditions from reported cases included diabetes; cancer; and chronic lung, heart, and kidney disease. § No vaccine currently available § Treatment is supportive and based on the patient’s clinical condition.  Prevention of Viral Infections: Vaccines - Vaccines are available to prevent over 13 viral infections of humans. Vaccines Types: 1. Live vaccines (attenuated ):contain weakened forms of the virus, which do not cause the disease but triggers immunity. Live vaccines can be dangerous when given to people with a weak immunity (immunocompromised). e.g. MMR vaccine 2. Killed vaccines: contain killed, but previously virulent, micro-organisms that have been destroyed with chemicals, heat, radioactivity or antibiotics. e.g. Influenza vaccine 3. Subunit vaccines: produced by biotechnology and genetic engineering techniques. These vaccines use only the capsid proteins of the virus. e.g. Hepatitis B vaccine Different types of vaccine A guide to vaccinology: from basic principles to new developments Schematic representation of different types of vaccine against pathogens; the text indicates against which pathogens certain vaccines are licensed and when each type of vaccine was first introduced. BCG, Mycobacterium bovis bacillus Nature Reviews Immunology (Nat Rev Immunol) ISSN 1474-1741 (online) ISSN 1474-1733  Treatment of Viral Infections (Anti-viral Drugs) § Until recent years, there were no drugs for the treatment of viral infections. § Antiviral drugs are difficult to develop and use because viruses are produced within host cells. § Antiviral drugs work by inhibiting viral replication inside cells, attachment, inhibit uncoating, and Inhibit DNA/RNA synthesis.