Medical Important Viruses - PDF
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İstinye University, Istanbul
Ayhan Mehmetoğlu
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This document presents a detailed overview of medical viruses, their structures, characteristics, and classifications. It touches upon viral diseases and groups, focusing on the categorization and structures.
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Medical important Viruses Asst. Prof. Ayhan Mehmetoğlu 1 Virus A virus is an infectious agent that is minimally constructed of two components: 1) a genome consisting of either ribonucleic acid (RNA) or deoxyribonucleic acid (DNA),...
Medical important Viruses Asst. Prof. Ayhan Mehmetoğlu 1 Virus A virus is an infectious agent that is minimally constructed of two components: 1) a genome consisting of either ribonucleic acid (RNA) or deoxyribonucleic acid (DNA), but not both, and 2) a protein-containing structure (capsid) designed to protect the genome. Many viruses have additional structural features, for example, an envelope composed of a protein-containing lipid bilayer, whose presence or absence further distinguishes one virus group from another. A complete virus particle combining these structural elements is called a virion. Virion In functional terms, a virion can be envisioned as a delivery system that surrounds a nucleic acid payload. The delivery system is designed to protect the genome and enable the virus to bind to host cells. The payload is the viral genome and may also include enzymes required for the initial steps in viral replication a process that is obligately intracellular. The pathogenicity of a virus depends on a great variety of structural and functional characteristics. Therefore, even within a closely related group of viruses, different species may produce significantly distinct clinical pathologies. 3 Dr. Ayham Abulaila 4 Virus Structure Viruses are approximately 100- to 1000-fold smaller than the cells they infect. The smallest viruses, virion size (parvoviruses), are approximately 20 nm in diameter (1 nm = 10–9 m), whereas the largest human viruses (poxviruses) have a diameter of approximately 300 nm and overlap the size of the smallest bacterial cells (Chlamydia and Mycoplasma). Therefore, viruses generally pass-through filters designed to trap bacteria, and this property can, in principle, be used as evidence of a viral etiology. 5 Dr. Ayham Abulaila 6 Characteristics Used to Define Virus Families, Genera, and Species Viruses are divided into related groups, or families, and, sometimes into subfamilies based on: 1) type and structure of the viral nucleic acid, 2) the strategy used in its replication, 3) type of symmetry of the virus capsid (helical versus icosahedral), and 4) presence or absence of a lipid envelope. Within a virus family, differences in additional specific properties, such as host range, serologic reactions, amino acid sequences of viral proteins, degree of nucleic acid homology, among others, form the basis for division into genera (singular = genus) and species 7 Dr. Ayham Abulaila 8 A. Genome It may be RNA or DNA, either of which may be single-stranded (ss) or double-stranded (ds). The most common forms of viral genomes found in nature are ssRNA and dsDNA. Single-stranded viral RNA genomes are further subdivided into those of positive polarity (that is, of messenger RNA sense, which can therefore be used as a template for protein synthesis), and those of negative polarity or are antisense (that is, complementary to messenger RNA sense, which cannot therefore be used directly as a template for protein synthesis). Viruses containing these two types of RNA genomes are commonly referred to as positive-strand and negative-strand RNA viruses, respectively. 9 B. Capsid symmetry The protein shell enclosing the genome is, for most virus families, found in either of two geometric configurations: helical (rod-shaped or coiled) or icosahedral (spherical or symmetric). The capsid is constructed of multiple copies of a single polypeptide type (found in helical capsids) or a small number of different polypeptides (found in icosahedral capsids), requiring only a limited amount of genetic information to code for these structural components. 10 Helical symmetry: Helical symmetry: Capsids with helical symmetry, such as the paramyxoviridae , consist of repeated units of a single polypeptide species that in association with the viral nucleic acid self-assemble into a helical cylinder. Each polypeptide unit (protomer) is hydrogen-bonded to neighboring protomers. The complex of protomers and nucleic acid is called the nucleocapsid. 11 Icosahedral symmetry Icosahedral symmetry: Capsids with icosahedral symmetry are more complex than those with helical symmetry, in that they consist of several different polypeptides grouped into structural subassemblies called capsomers. These, in turn, are hydrogen-bonded to each other to form an icosahedron. The nucleic acid genome is located within the empty space created by the rigid, icosahedral structure. 12 Dr. Ayham Abulaila 13 C. Envelope An important structural feature used in defining a viral family is the presence or absence of a lipid-containing membrane surrounding the nucleocapsid. This membrane is referred to as the envelope. A virus that is not enveloped is referred to as a naked virus. In enveloped viruses, the nucleocapsid is flexible and coiled within the envelope, resulting in most such viruses appearing to be roughly spherical. The envelope is derived from host cell membranes. However, the cellular membrane proteins are replaced by virus-specific proteins, conferring virus-specific antigenicity upon the particle. 14 Viral Replication; Replication Cycles of Viruses The individual steps in the virus replication cycle are presented below in sequence, beginning with virus attachment to the host cell and leading to penetration and uncoating of the viral genome. Gene expression and replication are followed by assembly and release of viral progeny. 15 Dr. Ayham Abulaila 16 Dr. Ayham Abulaila 17 Baltimore 7 groups classification of I: dsDNA: herpes, adeno, pox, papova Medically II: ssDNA: parvo Important III: dsRNA: reo, rota Viruses: IV: (+)ssRNA : picorna, toga, flavi, corona V: (-)ssRNA : rhabdo, orthomyxo, bunya, filo VI: (+)ssRNA-RT : retro, lenti VII: dsDNA-RT: Hepadna DNA Viruses The three naked (i.e., nonenveloped) icosahedral virus families—the parvoviruses, papovaviruses, and adenoviruses—are presented in order of increasing particle size, as are the three enveloped families. The hepadnavirus family, which includes hepatitis B virus, and the herpesviruses are enveloped icosahedral viruses. The largest viruses, the poxviruses, have a complex internal symmetry. 19 Papovaviruses These are naked icosahedral viruses (55 nm in diameter) with double-stranded circular supercoiled DNA. The name "papova" is an acronym of papilloma, polyoma, and simian vacuolating viruses. Three human papovaviruses are JC virus, isolated from patients with progressive multifocal leukoencephalopathy; BK virus, isolated from the urine of immunosuppressed kidney transplant patients; and human papillomavirus. 20 Adenoviruses These are naked icosahedral viruses (75 nm in diameter) with double-stranded linear DNA. They cause pharyngitis, upper and lower respiratory tract disease, and a variety of other less common infections. There are at least 40 antigenic types, some of which cause sarcomas in animals but no tumors in humans. 21 Hepadnaviruses These are double-shelled viruses (42 nm in diameter) with an icosahedral capsid covered by an envelope. The DNA is a double-stranded circle that is unusual because the complete strand is not a covalently closed circle and the other strand is missing approximately 25% of its length. Hepatitis B virus is the human pathogen in this family. 22 Herpesviruses These are enveloped viruses (100 nm in diameter) with an icosahedral nucleocapsid and double-stranded linear DNA. They are noted for causing latent infections. The five important human pathogens are herpes simplex virus types 1 and 2, varicella- zoster virus, cytomegalovirus, and Epstein- Barr virus (the cause of infectious mononucleosis). 23 Dr. Ayham Abulaila 24 Poxviruses These are the largest viruses, with a bricklike shape, an envelope with an unusual appearance, and a complex capsid symmetry. They are named for the skin lesions, or "pocks," that they cause. Smallpox virus and vaccinia virus are the two important members. The latter virus is used in the smallpox vaccine. 25 RNA Viruses The three naked icosahedral virus families are listed first and are followed by the three enveloped icosahedral viruses. The remaining eight families are enveloped helical viruses; the first five have single- stranded linear RNA as their genome, whereas the last three have single-stranded circular RNA. 26 Picornaviruses These are the smallest (28 nm in diameter) RNA viruses. They have single-stranded, linear, nonsegmented, positive-polarity RNA within a naked icosahedral capsid. The name "picorna" is derived from pico (small), RNA-containing. There are two groups of human pathogens: (1) enteroviruses such as poliovirus, coxsackievirus, echovirus, and hepatitis A virus and (2) rhinoviruses. 27 Caliciviruses These are naked viruses (38 nm in diameter) with an icosahedral capsid. They have single-stranded, linear, nonsegmented, positive-polarity RNA. There are two human pathogens: Norwalk virus and hepatitis E virus. Taxonomists have recently placed hepatitis E virus into its own genus called hepevirus. 28 Reoviruses These are naked viruses (75 nm in diameter) with two icosahedral capsid coats. They have 10 segments of double-stranded linear RNA. The name is an acronym of respiratory enteric orphan, because they were originally found in the respiratory and enteric tracts and were not associated with any human disease. The main human pathogen is rotavirus, which causes diarrhea mainly in infants. 29 Flaviviruses These are enveloped viruses with an icosahedral capsid and single- stranded, linear, nonsegmented, positive-polarity RNA. The flaviviruses include hepatitis C virus, yellow fever virus, dengue virus, West Nile virus, and St. Louis and Japanese encephalitis viruses. 30 Togaviruses These are enveloped viruses with an icosahedral capsid and single-stranded, linear, nonsegmented, positive-polarity RNA. There are two major groups of human pathogens: the alphaviruses and rubiviruses. The alphavirus group includes eastern and western encephalitis viruses; the rubivirus group consists only of rubella virus. 31 Retroviruses These are enveloped viruses with an icosahedral capsid and two identical strands (said to be "diploid") of single-stranded, linear, positive- polarity RNA. The term "retro" pertains to the reverse transcription of the RNA genome into DNA. There are two medically important groups: (1) the oncovirus group, which contains the sarcoma and leukemia viruses, e.g., human T-cell leukemia virus (HTLV) and (2) the lentivirus ("slow virus") group, which includes human immunodeficiency virus (HIV) and certain animal pathogens 32 Orthomyxoviruses These viruses (myxoviruses) are enveloped, with a helical nucleocapsid and eight segments of linear, single-stranded, negative- polarity RNA. The term "myxo" refers to the affinity of these viruses for mucins, and "ortho" is added to distinguish them from the paramyxoviruses. Influenza virus is the main human pathogen. 33 Paramyxoviruses These are enveloped viruses with a helical nucleocapsid and single-stranded, linear, nonsegmented, negative-polarity RNA. The important human pathogens are measles, mumps, parainfluenza, and respiratory syncytial viruses. 34 Rhabdoviruses These are bullet-shaped enveloped viruses with a helical nucleocapsid and a single-stranded, linear, nonsegmented, negative-polarity RNA. The term "rhabdo" refers to the bullet shape. Rabies virus is the only important human pathogen. 35 Filoviruses These are enveloped viruses with a helical nucleocapsid and single- stranded, linear, nonsegmented, negative-polarity RNA. They are highly pleomorphic, long filaments that are 80 nm in diameter but can be thousands of nanometers long. The term "filo" means "thread" and refers to the long filaments. The two human pathogens are Ebola virus and Marburg virus. 36 Coronaviruses These are enveloped viruses with a helical nucleocapsid and a single-stranded, linear, nonsegmented, positive-polarity RNA. The term "corona" refers to the prominent halo of spikes protruding from the envelope. Coronaviruses cause respiratory tract infections, such as the common cold and SARS (severe acute respiratory syndrome), in humans, COVID-19. SARS-Cov-1(2003), MERS (2012), SARS-Cov- 2(2020) 37 Coronaviruses and Covid-19 1 Diseases Coronaviruses are an important cause of the common cold, probably second only to rhinoviruses in frequency. In 2002,a new disease, an atypical pneumonia called severe acute respiratory syndrome (SARS), emerged. In 2012, another severe pneumonia called Middle East respiratory syndrome (MERS) emerged. In 2020, another pneumonia causing corona virus called SARS-cov-2 which cause COVID-19 disease emerged. 3 9 https://doi.org/10.1111/jsap.13207 SARS 2002 SARS originated in China in November 2002 and spread rapidly to other countries. There have been 8300 cases and 785 deaths—a fatality rate of approximately 9%. Human-to-human transmission occurs, and some patients with SARS are thought to be “super-spreaders.” Early in the outbreak, many hospital personnel were affected, but respiratory infection control procedures have greatly reduced the spread within hospitals. The horseshoe bat appears to be the natural reservoir for CoV-SARS, with the civet cat serving as an intermediate host. 42 MERS In 2012–2013, a new human coronavirus caused an outbreak of serious, often fatal pneumonia in Saudi Arabia and other countries in the region. The disease is called Middle East respiratory syndrome (MERS), and the virus is called MERS coronavirus (MERS-CoV). Its closest relative is a bat coronavirus, and bats are thought to be a reservoir. Close contact with camels appears to be the mode of transmission to humans. The risk of person-to-person transmission is low but has occurred in hospitals with inadequate infection control. Another name for the virus is human coronavirusEMC (HCoV-EMC) 43 COVID-19 The 2019–20 coronavirus pandemic is a pandemic of coronavirus disease 2019 (COVID-19). The disease was first identified in Wuhan, Hubei, China in December 2019. Disease: Coronavirus disease 2019 (COVID-19). Virus strain: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Incubation period: 1-14 days (6 days in general) 23 11 March 2020, WHO declared COVID-19 as a pandemic Schematic representations of SARS-CoV-2 genome organisation, gene expression strategy and virion structure From: SARS-CoV-2/COVID-19: a primer for cardiologists https://doi.org/10.1007/s12471-020-01475-1 Symptoms of Covid-19 The most common symptoms of COVID-19 are fever, tiredness, and dry cough. Some patients may have aches and pains, nasal congestion, runny nose, sore throat or diarrhea. These symptoms are usually mild and begin gradually. Some people become infected but don’t develop any symptoms and don't feel unwell. Most people (about 80%) recover from the disease without needing special treatment. 29 Sever symptoms Around 1 out of every 6 people (16%) who gets COVID-19 becomes seriously ill and develops difficulty breathing. Older people, and those with underlying medical problems like, are more likely to develop serious illness. high blood pressure, heart problems or diabetes People with fever, cough and difficulty breathing should seek medical attention. 34 Trends Immunol. 2020 Dec; 41(12): 1100–1115. https://kyxy.radio.com/blogs/kyxy/coronavirus-2019-ncov-safety-advices-and-tips43 COVID-19 vaccines As of 18 February 2021, at least seven different vaccines across three platforms have been rolled out in countries. Pfizer-BioNTech COVID-19 vaccine mRNA Moderna’s COVID-19 vaccine mRNA The Johnson & Johnson Sinovac vaccine inactivated virus COVID-19 Sinopharm vaccine inactivated virus Vaccine viral vector Oxford astrazeneca vaccine viral vector One dose Sputnic vaccine viral vector Novavax vaccine protein-based (B.1.1.529): SARS-CoV-2 Summary The classification of viruses is based primarily on the nature of the genome and whether the virus has an envelope. Poxviruses, herpesviruses, and hepadnaviruses are DNA viruses with an envelope, whereas adenoviruses, papovaviruses, and parvoviruses are DNA viruses without an envelope, i.e., they are naked nucleocapsid viruses. Parvoviruses have single-stranded DNA, whereas all the other families of DNA viruses have double-stranded DNA. The DNA of hepadnaviruses (hepatitis B virus) is mostly double- stranded but has a single-stranded region. 55 Summary Picornaviruses, caliciviruses, and reoviruses are RNA viruses without an envelope, whereas all the other families of RNA viruses have an envelope. Reoviruses have double-stranded RNA; all the other families of RNA viruses have single-stranded RNA. Reoviruses and influenza viruses have segmented RNA; all the other families of RNA viruses have nonsegmented RNA. Picornaviruses, caliciviruses, flaviviruses, togaviruses, retroviruses, and coronaviruses have positive-polarity RNA, whereas all the other families have negative-polarity RNA. 56 Refernces Lippincotts Illustrated Reviews Microbiology 3rd Edition by Richard A. Harvey Cynthia Nau Cornelissen_Ph.D Clinical and Diagnostic Virology (Canbridge, 2009) Jawetz Melnick & Adelbergs Medical Microbiology Review of Medical Microbiology and Immunology, Fourteenth Edition by Warren Levinson, MD, PhD. For any question [email protected] 58