Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
RESPIRATORY VIRUSES What is a virus? Viruses are not cells. They cannot synthesise their own energy or proteins and are not capable of independent replication. They are dependent on a host cell. How do they differ from prokaryotes and eukaryotes? they are composed of an internal core containing DNA or RNA, not both. This is covered by a protective protein coat. Some have an outer lipoprotein membrane (envelope). They do not contain any organelles Viruses can only reproduce within the host cell because they cannot synthesise energy or make proteins viruses do not replicate using the mechanisms of binary fission or mitosis. One virus can produce hundreds more viruses. Refer to Lange (2008) p.192 for table Viruses have varying shapes and sizes. The shape is determined by the repeating sub units that form the protein coat called a capsid. Nucleic Acid Make Up can be singe or double stranded DNA or RNA nucleic acid can be linear or circular DNA is always single molecule RNA can be single molecule or exist in several pieces the nucleic acid of the virus is surrounded by a protein coat (capsid) the capsid is made up of subunits called capsomes. In some viruses the capsid is the outer layer o the virus. These are called naked viruses. In some viruses the capsid is surrounded by a lipoprotein cover called an envelope, which becomes the surface of the virus. The capsomes and the nucleic acid form a structure called the nucleocapsid The repeating subunits of the capsid give the virus its shape and so is used when classifying viruses. Spherical viruses are said to have icosahedral symmetry and others are said to have helical symmetry. viruses that infect humans are helical and are enveloped. viruses only have one copy of their genome (haploid) except retroviruses (diploid) Viral Proteins surface proteins help the virus attach to host cell receptors. This determines host specificity and organ specificity of the virus. these surface proteins are the targets for antibodies. The antibodies bind to these surface protein and prevent them from attaching to the cell receptor so inhibits (neutralises) viral infection. internal proteins can include DNA or RNA polymerase in enveloped viruses the matrix protein mediates interaction between viral nucleocapsid and envelope proteins (surface protein) some viruses produce antigenic variants of surface proteins. This allows them to invade our immune defenses because we may produce antibodies against one antigenic variant (serotype) but not another * Enveloped viruses acquire their envelope as they exit the host cell. This process is called budding viruses that have an envelope are less stable as they are more easily inactivated. They are generally more sensitive to heat, drying, detergents and lipid solvents such as alcohol. nearly all viruses transmitted via faecal-oral route are naked whereas viruses such as HIV, HBV and HCV are enveloped and transmitted via blood or sexual transmission Viral Growth Cycle One virion (1 virus particle) can replicate in approximately 10hrs to produce hundreds of virions within that cell. Refer to Lange (2008) p.199 for growth curve. when the virion enters the cell and infects it, it changes cell morphology and affects cell fx causing a cytopathic effect (CPE) which results in cell lyses and death. Not all viruses cause CPE, some can replicate and have little effect on changes to cell morphology or fx. Stages of viral growth cycle (Lange 2008) 1. Attachment and penetration by parental virion 2. Uncoating of the viral genome 3. Early viral mRNA synthesis 4. Early viral protein synthesis 5. Viral genome replication 6. Late viral mRNA synthesis 7. Late viral protein synthesis 8. Progeny virion assembly 9. Virion release from cell Some viruses have surface proteins that attach to specific cells and or organs. E.g HIV attaches to CD4 protein on T Helper lymphocytes the virus enters the cell via pinocytotic vesicles which engulf it and takes it into the cell the receptors for viruses on the cell have other normal fx. Eg. vaccinia virus binds to the receptor for epidermal growth factor All viruses are infectious but not all purified viral DNA or RNA (genomes) are infectious. If they are infectious it means that they are able to replicate and carry out the entire viral growth cycle, generating complete virus particles. DNA viruses replicate in the nucleus. RNA viruses replicate in the cytoplasm except retroviruses and influenza which partly replicate in the nucleus. RNA Viruses Categorised into 4 groups that differentiate how they synthesise mRNA 1. positive polarising single stranded RNA which uses its single strand as its genetic material. Positive polarity is RNA with the same basic sequence as mRNA. Eg. if mRNA is ACUG, it will ACUG 2. negative polarity single strand means mRNA must be transcribed by using the negative strand as a template. Negative polarity is RNA with base sequence complimentary to mRNA Eg. if mRNA is ACUG, it is UGAC 3. double stranded RNA. This virus carries its own polymerase to transcribe to mRNA 4. Single stranded RNA of positive polarity that is transcribed into double stranded DNA. This is then transcribed to viral mRNA by host cell's regular RNA polymerase. Only viruses that do not require polymerase have infectious nucleic acid. Major groups of viruses infecting the respiratory system Influenza RNA virus, negative polarity genome, helical nucleocapsid, lipoprotein envelope orthomyxovirus – segmented RNA genome. “myxo” means it interact with glycoproteins on the surface of the cell. smaller in size than paramyxoviruses the envelope is covered with 2 different types of spikes haemogglutinin (H) its fx is to bind to cell surface receptor to initiate infection neuraminidase (N) its fx is to cleave neuraminic acid (sialic acid) to release progeny viruses from the infected cell. It degrades the protective layer of mucus in the respiratory tract. This enables it to infect the respiratory epithelium. Influenza viruses especially influenza A can change in their antigenic variant of H and N proteins contributing to their ability to cause epidemics. Antigenic variation occurs because of: antigenic shifts – major changes in the re assortment of segments of genome RNA antigenic drifts – minor changes based on mutations in genome RNA Influenza has 2 matrix proteins. M1 protein resides between internal nucleoprotein segments an envelope and provides structural support. M2 matrix proteins form virion channels between the interior of the virions and the external environment. M2 plays a role in allowing virions to uncoat and allow the nucleocapsid to migrate into the nucleus of the cell. Antigens on influenza are both group specific and type specific. Internal ribnucleoprotein is group specific A,B,C H and N are type specific and located on the surface Antibodies against the H neutralises it and prevents infection by antibodies against the group do not prevent infection Antibodies against N do not neutralise it but helps to reduce disease. Replication virion absorbed into cell when H interacts with sialic acid receptors virus uncoats within an endosome (vesicle formed during pinocytosis) protons pass through M2 protein into interior of virion. This frees nucleocasids to enter cytoplasm and migrate into the nucleus replicates in nucleus Transmission of influenza – airborne respiratory droplets Infection is limited to upper and lower respiratory tract as the proteases that cleave the H are located in the respiratory tract. Signs and symptoms fever myalgia headache sore throat cough Symptoms usually resolve within 4-7 days Lab Dx – nasal or throat swabs, sputum, antibodies in serum Treatment Amantadine – blocks M2 ion channels but in US 90% are resistant Paramyxoviruses Measles, mumps, respiratory syncytial virus (RSV), parainfluenza virus differ from orthomyxoviruses because genome is not segmented surface spikes are different composed of one single stranded RNA helical nucleocapsid and outer lipoprotein envelope virion contains RNA polymerase which transcribes the negative polarity genome into mRNA. Genome is not infectious envelope covered with spikes that contain H and N or a fusion protein that causes cell fusion or haemolysis Measles maculopapular rash, occurs mostly in childhood has H and fusion protein that causes haemolysis has single serotype (antigenic variant). Antibody is directed at H antigen Humans are hosts Transmitted via respiratory droplets – coughing and sneezing after infecting cells of upper respiratory tract, it enters blood then to the skin after rash appears, the virus can no longer be spread to others life long immunity develops after the person has disease Signs and symptoms fever conjunctivitis running nose coughing rash appears on face and proceeds down body to hands and feet Treatment – no antiviral available Immunisation with live attenuated vaccine. Mumps Parotid gland swelling. Mostly in childhood single serotype antibody directed at H transmitted via respiratory droplets infects upper respiratory tract then spreads to blood then parotid glands, testes, ovaries, pancreas, meninges lifelong immunity occurs to those who have had the disease Signs & symptoms fever malaise anorexia swelling of parotid glands (uni-lateral or bilateral) Usually resolves within one week No antiviral treatment Immunisation with live attenuated vaccine Respiratory Syncytial Virus (RSV) cause of pneumonia and bronchitis in infants causes otitis media in children causes pneumonia in elderly and people with chronic cardiopulmonary disease surface spikes are fusion proteins that cause cells to fuse forming multinucleated giant cells (syncytia) 2 serotypes A and B Antibodies target fusion protein Similar transmission to measles and mumps RSV causes common colds and respiratory tract infections in normal adult population No vaccine available Parainfluenza Virus causes croup, laryngitis, bronchiolitis and pneumonia in children. In adults resembles colds surface protein contain H, N and fusion proteins Humans and animals are infected but animal strains do not infect humans transmitted via same path as other paramyxoviruses can cause croup in children under 5 – harsh cough and hoarseness no antiviral or vaccine Coronaviruses Causes common colds non segmented single stranded RNA helical nucleocapsid, enveloped 2 serotypes SARS is an example Replication absorbed into the cell via H. Enters into cytoplasm. Positive strand genome is translated to 2 large polypeptides which are self cleaved by virus encoded protease the virus is assembled and obtains its envelope from cytoplasmic reticulum. Replication occurs in the cytoplasm Transmitted via respiratory aerosol Coronaviruses are limited to mucosal cells of the respiratory tract immunity following infection appears brief and reinfection can occur Pneumonia caused by SARS is characterised by oedema then hypoxia. Signs and Symptoms running nose scratchy sore throat low grade fever typically lasts several days may cause bronchitis SARS is atypical fever from 38 degrees non productive cough dyspnoea hypoxia chills rigors malaise sore throat and running nose uncommon No antiviral or vaccine available SARS has been experimentally treated with ribavirin and steroids however ???? effectiveness. Adenoviruses Naked icosahedral viruses with double stranded linear DNA causes pharyngitis, URTI and LRTI PBL – Magic Bullets What caused this lady to be susceptible to bacterial pneumonia? She had a viral infection which left her immunosupressed Her mucus membrane in the respiratory tract was already attacked by the virus previously and leaves it open to strep. pneumoniae bacteria being in hospital caused hospital acquired pneumonia (nocosomial) pneumonia.