Basic Virology - RNA Viruses: Coronavirus PDF

RNA Viruses: Coronavirus Helen Kalandarishvili UG 2023  MRNA S T - 5 3 RNA VIRUSES PLAS-STRANDED RNA VIRUSES...

RNA Viruses: Coronavirus Helen Kalandarishvili UG 2023  MRNA S T - 5 3 RNA VIRUSES PLAS-STRANDED RNA VIRUSES ↑ 51 3/ ⑦ - - #5. > 3- ↓ MRNA Single stranded RNA viruses are classified as positive or negative depending on the sense or polarity of the RNA Positive-strand RNA virus: Also known as a sense-strand RNA virus, a virus whose genetic information consists of a single strand of RNA that is the positive (or sense) strand which encodes mRNA (messenger RNA) and protein. Replication in positive-strand RNA viruses is via a negative-strand intermediate.  CORONAVIRUSES Coronaviruses are large, Worldwide spread enveloped RNA viruses. Human coronaviruses cause ✓ common colds( by L no frequency 2nd only specific virus that causes it to rhinovirus) ✓ gastroenteritis in infants. Animal coronaviruses cause diseases of - economic importance in domestic animals Animal coronaviruses may be the source of Human coronaviruses are difficult to human infection. culture and therefore are poorly characterized CORONAVIRUSES Epidemics and pandemics 2002 - worldwide outbreak of a new disease, an atypical pneumonia - severe acute respiratory syndrome (SARS). 2003 - a novel coronavirus was identified: Causative agent of SARS- SARS-CoV 2012 - a new coronavirus emerged: MERS-CoV Middle East respiratory syndrome (MERS) - severe pneumonia 2019 - New severe respiratory infection with pneumonia and respiratory distress- CoViD 19 ▪ New strain of coronaviruses – CoVid19 or SARS-CoV-2 CORONAVIRUSES TEM images: CoVSARS and CoVMERS SARS MERS CORONAVIRUSES Structure & Composition Coronaviruses are enveloped, 120- to 160-nm particles Helical nucleocapsid 9–11 nm in diameter. 20-nm club-or petal-shaped projections widely spaced on outer surface of envelope- a “solar corona”. Nonsegmented, single-stranded, Two serotypes called 229E and OC43 positive-polarity RNA genome; Genome sequence of the SARS (CoV-SARS) coronavirus is different from existing human strains, but very similar for different SARS (CoV-SARS) isolates - antigenicity is likely to be quite stable. - enveloped > - resistant to heat acid , , etc. CORONAVIRUSES Characteristics Morphology: “Crown-like” appearance under EM Genome: 80~160nm, ssRNA(+), 27-31 kb (larger genome among RNA viruses) Sensitive to acid, ether, drying, heating to 56ºC, optimum temperature for virus:33~35ºC Proteins Function E1 (Membrane glycoprotein) Budding, envelope formation E2 (Spike glycoprotein) R. binding, cell fusion, as Ag E3 (Hemagglutinin-acetylesterase gp) Combined with influenza C N (Nucleocapsid phosphoprotein) Ribonucleoprotein CORONAVIRUSES ✓ Human coronaviruses do not grow well in cell culture and therefore are not well characterized Replication ✓ Details of viral replication obtained from mouse hepatitis virus- closely related to human strain OC43 The Virus replicates in the cytoplasm - The particle is then Virus attaches to receptors on internalized, probably by target cells by glycoprotein Functional receptor for the absorptive endocytosis. spikes on the viral envelope SARS CoV is angiotensin- (either by S or HE). converting enzyme 2 ( ACE-2) The S glycoprotein may cause fusion ✓ the same receptor for CoVid 19 virus of the viral envelope with the cell ✓ MERSCoV binds to CD-26 on the membrane leading to uncoating. respiratory mucosa, Requires pH 6.5 or higher ✓ Receptor for human coronavirus 229E ! aminopeptidase N CORONAVIRUSES Replication Newly synthesized genomic RNA molecules interact in the cytoplasm with the nucleocapsid protein to form helical nucleocapsids Translation of viral Mature virions transported in genomic RNA vesicles to the cell periphery for exit or may be released upon cell lysis. ✓ produce a virus-specific RNA- The nucleocapsids bud through dependent RNA polymerase. membranes of the rough ✓ Viral polymerase transcribes a full- endoplasmic reticulum and the Golgi length complementary (minus- apparatus in areas that contain the strand) RNA –a template for a set viral glycoproteins. of 5-7 subgenomic mRNAs. CORONAVIRUSES Replication Coronaviruses exhibit a high frequency of mutation during each round of replication, ! Coronaviruses undergo a high frequency of generation of a high incidence of deletion recombination during replication; mutations. All this is unusual for an RNA virus with a nonsegmented genome and may contribute to ! evolution of new virus strains. CORONAVIRUSES CORONAVIRUSES Classification The Coronaviridae family is classified within the order Nidovirales. Six genera : Two subfamilies: ✓ Alphacoronavirus, ✓ Betacoronavirus, ✓ Coronavirinae ✓ Gammacoronavirus, ✓ Torovirinae ✓ Deltacoronavirus, ✓ Bafinivirus, ✓ Torovirus Characteristics used to classify Coronaviridae: - particle morphology, - unique RNA replication strategy, - genome organization, - nucleotide sequence homology. CORONAVIRUSES Classification Able to infect humans Three genera: ✓ Alphacoronavirus, The toroviruses are widespread in ✓ Betacoronavirus ungulates (herbivore animals with ✓ Torovirus hooves) and appear to be associated with diarrheal disease Two serogroups of human coronaviruses, represented by strains 229E and OC43. Third distinct antigenic group SARS virus can be placed in the same group (Group 2) contains the avian infectious as OC43. bronchitis virus of chickens CORONAVIRUSES Human Coronaviruses Seven(7) coronaviruses are known that can infect humans ✓ isolated form patients (sporadic case or ourtbreaks) alpha –coronaviruses ! beta –coronaviruses ! 229E and NL63 OC43, HKU1, SARS-CoV, MERS-CoV, COVID-19 HCoV-229E and HCoV-OC43 are thought to account for 5 - 30% of human respiratory tract infections, CoV-NL63 and HCoV-HKU1 were detected in ~5% of respiratory tract samples CORONAVIRUSES Epidemiology Coronaviruses are distributed worldwide Outbreaks occur primarily in the winter on a 2- to 3-year cycle They are transmitted by the respiratory aerosol. Infection is typically limited to the mucosal cells of the respiratory tract Approximately 50% of infections are asymptomatic Immunity following infection appears to be brief, and reinfection can occur. CORONAVIRUSES Where did SARS-CoV come from? Chinese horseshoe bats are natural reservoirs of SARS-like coronaviruses, also now for CoVid 19 coronavirus In rural regions of southern China, people, pigs, and domestic fowl live close together Widespread use of wild species for food and traditional medicine— conditions that promote the emergence of new viral strains SARS-CoV horseshoe bats The complete 29,727-nucleotide sequence of RNA genome of SARS-CoV proves the new viral family Each gene of SARS-CoV has only 70% or less identity with the corresponding gene of known coronavirus SARS-CoV belong to neither of current 3 groups It is likely that SARS-CoV was enzootic in an animal species and had been genetically isolated for a very long time before suddenly emerging as a virulent human virus palm civets CORONAVIRUSES Where did MERS come from? MERSCoV likely originated in bats and became widespread in Juvenile camels- key camels(showed seropositivity for MERS CoV). source of MERS Contact with either bats or camels may lead to initial human infections, which can then be transmitted from person to person CORONAVIRUSES Where did CoVID -19 come from? Origin story of coronavirus CoVid19: in late 2019 someone at the Huanan seafood market in Wuhan, China was infected with a virus from an animal bat The primary source – most likelybagain a bat The pangolin –a scaly mammal is supposed to be the staging post for the virus before it spread to humans. Viruses of this type are circulating all the time in the animal kingdom. pangolin CORONAVIRUSES Human Coronaviruses (except SARS - MERS - CoV19) cause 15–30% of all common colds and have been implicated in gastroenteritis in infants. Death from progressive respiratory failure occurs in almost 10% of cases, with the death rate highest among the elderly. The incubation period is from 2 days to 5 days, and symptoms usually last about 1 week. Common early symptoms include fever, malaise, chills, headache, dizziness, cough, and sore throat, followed a few days later by shortness of breath. The lower respiratory tract is seldom involved. Clinical features of coronavirus-associated enteritis have not been clearly described. CORONAVIRUSES SARS Recovered in 2003 from patients with severe acute respiratory syndrome (SARS) The outbreak erupted in southern China in late 2002 by mid-2003 had resulted in over 8000 cases in 29 countries, with over 800 deaths (case fatality rate of 9.6%). a Pneumonia-lung inflammed * typical Pneumonia to alroi > - no oxygen L edema goes ✓ Human-to-human transmission > - ✓ Incubation period 2-10 days ✓ Fever, headache, chills, sore throat, cough, shortness of breath. ✓ May progress to acute respiratory distress, requiring ventilator support. Death from progressive respiratory failure occurs in 10%. ✓ Severe atypical pneumonia caused by SARS is characterized by diffuse edema resulting in hypoxia. The binding of the virus to angiotensin-converting enzyme-2 on the surface of respiratory tract epithelium may contribute to the dysregulation of fluid balance that causes the edema in the alveolar space. ✓ Chest X-ray reveals interstitial “ground-glass” infiltrates that do not cavitate. Leukopenia and - - decrease leukoutes thrombocytopenia are seen. - Ldecrease place leto CORONAVIRUSES MERS Middle East respiratory syndrome - Identified in 2012 in Saudi Arabia in patient who died of respiratory failure. ✓ Caused outbreaks in South Korea in 2015 and in Saudi Arabia in 2018 ✓ Over 2,500 cases have been reported as of January 2021, including 45 cases in the year 2020. About 35% of those who are diagnosed with the disease die from it. ✓ MERS-CoV is a coronavirus believed to be originally from bats. However, humans are typically infected from camels, either during direct contact or indirectly. Spread between humans typically requires close contact with an infected person. Causes mild to severe respiratory illness. Incubation 2-13 days Human-to-human transmission Extended illness in some cases leads to pneumonia and death. Enteritis are similar to rotavirus infections. CORONAVIRUSES Serological Testing ✓ IFA: Indirect fluorescent antibody ✓ ELISA: Enzyme-linked immunosorbent assays Diagnosis Molecular Testing ✓ RT-PCR: Reverse transcriptase-PCR ✓ Can detect infection within the first 10 days No proven treatment. Treatment antivirals and interferons (ribavirin + interferon alfa-2a or interferon alfa-2b) nor corticosteroids improved outcomes No vaccine. Under development.  CORONAVIRUSES COVID-19 “Wuhan coronavirus” S same betaCoVs subfamily SARS-CoV-2 - genetically linked to SARS CoV virus C, ss RNA(+) virus Enveloped (International Committee on Taxonomy of Viruses) L sensitive to heat , acid , 27 Genome ~28,5 kbp Covid 19 virus (WHO) Round or elliptic and often pleomorphic form, D= ~80 - 140nm. ~15nm Sensitive to ultraviolet rays and heat. Can be effectively inactivated by lipid solvents, including ether, ethanol, chlorine-containing disinfectant, chloroform TEM picture ( India) CORONAVIRUSES COVID-19 Infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease was first identified in December 2019 in Wuhan, and has since spread globally, resulting in the coronavirus pandemic Common symptoms include: ▪ fever, cough, and shortness of breath ▪ muscle pain, sputum production, diarrhea, sore throat, loss of smell, and abdominal pain. Majority of cases result in mild symptoms Some progress to viral pneumonia and multi-organ failure CORONAVIRUSES COVID-19 The virus is spread: ▪ during close contact ▪ by small droplets produced when people cough, sneeze, or talk ▪ by touching a contaminated surface and then their face. Virus is not generally airborne The virus can survive on surfaces up to 72 hours. Incubation time 2-14 days, with an average of five days It is most contagious during: ▪ the first 3 days after onset of symptoms ▪ before symptoms appear ▪ in later stages of the disease CORONAVIRUSES Treatment Diagnosis There is no proven antiviral treatment for human coronavirus infections Potential drugs: Combination of symptoms, risk Ribavirin factors and a chest CT ✓ Currently used for RSV and HCV infection ✓ A purine nucleoside analogue For SARS: not rRT-PCR from a nasopharyngeal assured swab ✓ Protease inhibitors used in the treatment of HIV infections (eg, lopinavir) have in vitro activity against SARS coronavirus Remdesivir –drug initially developed for Ebola in clinical trials for CoViD19 CORONAVIRUSES Immunity Immunity develops but is not absolute. Immunity against the surface projection antigen is most important Resistance to reinfection may last several years Reinfections with similar strains are common. >95% of patients with SARS or MERS developed an antibody response to viral antigens detectable by a fluorescent antibody test or ELISA. CORONAVIRUSES Prevention ✓ Frequent hand washing ✓ Social distancing ✓ Covering coughs and sneezes with a tissue or inner elbow ✓ Keeping unwashed hands away from the face ✓ Using of masks for those who suspect they have the virus ✓ There are several vaccines ✓ Management involves treatment of symptoms, supportive care, isolation, and experimental measures CORONAVIRUSES Approved vaccines (FDA, Vaccines -7 body recognizes it > WHO) jantigen produces antibodies Pfizer-BioNTech People 16 years and older ViralC vector vaccines ! 2 shots ( +1 +1 booster) Oxford Astrazeneka Given 3 weeks (21 days) apart Messenger RNA ( mRNA) - 2 weeks after second shot vaccines ! Moderna Pfeizer-BioNTech, Moderna Inactivated coronavirus People 18 years and older vaccine ! 2 shots(+ booster) Sinopharm , Sinovac Given 4 weeks (28 days) apart 2 weeks after second shot Oxford Astrazeneka WHO meeting (March 2023): People 18 years and older ✓ it was likely that the effectiveness of vaccines based on 2 shots the index virus would reduce over time. Given 8-12 weeks apart ✓ therefore WHO advised vaccine manufacturers and 2 weeks after second shot regulatory authorities to consider an update of vaccine Johnson & Johnson’s Janssen antigen composition by including Omicron, as the most People 18 years and older antigenically distinct SARS-CoV-2 variant thus far, for 1 shot administration as a booster dose. 2 weeks after shot  RNA VIRUS ORTHOMYXOVIRUSES Helen Kalandarishvili UG 2023  NEGATIVE-STRANDED - RNA VIRUSES The virion RNA is negative sense (complementary to mRNA) and must therefore be copied into the complementary plus-sense mRNA before proteins can be made. Because the cell does not have an RNA polymerase capable of using RNA as a template, the virus carries its own RNA-dependent RNA polymerase. There are two subcategories of negative-polarity RNA viruses: ▪ those that have a single piece of RNA (paramyxovirus or rabies virus) ▪ those that have multiple pieces of RNA (influenza virus).  Paramyxoviruses Enveloped - RNA VIRUSES Orthomyxoviruses Orthomyxoviruses Paramyxoviruses Filoviruses Rhabdoviruses Bunyaviruses Arenaviruses Filoviruses Arenaviruses Bunyaviruses Rhabdoviruses ORTHOMYXOVIRUSES Name originates from the Greek word ortho (correct), myxo (mucus). Essentially virions infect epithelial cells the right way. Influenza viruses are a major determinant of morbidity and mortality caused by respiratory disease, and - outbreaks. Mutability and high frequency of genetic reassortment and resultant antigenic changes make influenza viruses formidable challenges for control efforts. Influenza type: ✓ A is antigenically highly variable and is responsible for most cases of epidemic influenza. Jeause biggest outbreaks ✓ B may exhibit antigenic changes and sometimes causes epidemics. ✓ C is antigenically stable and causes only mild illness in immunocompetent individuals. ✓ D primarily affect cattle and are not known to infect or cause illness in people ORTHOMYXOVIRUSES Influenza Virions Infecting Epithelial Cells (Upper Resp. Tract) L biggest pool of host ↳ transmitted bet host ORTHOMYXOVIRUSES Influenza virus is composed of: ✓ a segmented single-stranded RNA genome ✓ a helical nucleocapsid ✓ an outer lipoprotein envelope envelope is covered with two different types of spikes, a hemagglutinin and a neuraminidase - - 16 antigenically distinct types of hemagglutinin (HA) - - important proteins 9 antigenically distinct types of neuraminidase (NA). - Virion contains an RNA-dependent RNA polymerase ORTHOMYXOVIRUSES ORTHOMYXOVIRUSES The two surface antigens of influenza undergo antigenic variation independent of each other. Antigenic variations in the surface glycoproteins, HA and NA, are used to subtype the viruses. Only type A has designated subtypes. ORTHOMYXOVIRUSES Classification Influenza A viruses are classified by subtypes based on the properties of their hemagglutinin (H) and neuraminidase (N) surface proteins. There are 16-18 different HA subtypes and 9-11 different NA subtypes. Subtypes are named by combining the H and N numbers – e.g., A(H1N1), A(H3N2). Influenza B viruses are further classified into two lineages: B/Yamagata and B/Victoria ORTHOMYXOVIRUSES ORTHOMYXOVIRUSES - Neuramidase 1 - Hemaglutinnin 1 - ORTHOMYXOVIRUSES Replication Influenza A virus has two matrix proteins: M1 matrix protein - located between the internal nucleoprotein and the envelope and provides structural - > I make the envelope integrity. - M2 matrix protein forms an ion channel between the interior of the virus and the external milieu. ✓ This ion channel plays an essential role in the uncoating of the virion after it enters the cell. · no uncoating > no replication - ✓ It transports protons into the virion causing the disruption of the envelope, which frees the nucleocapsid containing the genome RNA, allowing it to migrate to the nucleus. ORTHOMYXOVIRUSES Replication Influenza viruses have both group-specific and type-specific antigens ▪ e The internal ribonucleoprotein (complex of ribonucleic acid and RNA-binding protein) is the group-specific antigen that distinguishes influenza A, B, and C ▪ - The hemagglutinin and the neuraminidase are the type-specific antigens located on the surface. Antibody against the hemagglutinin neutralizes the infectivity of the virus (and prevents disease) Antibody against the group-specific antigen (which is located internally) does not. Nonstructural protein called NS 1 - an important determinant of the virulence ✓ NS 1 has several functions ! Inhibition of the production of interferon mRNA. ORTHOMYXOVIRUSES Replication Hemagglutinin binds to the cell surface receptor (neuraminic acid, sialic acid) to initiate infection of the cell. ✓ hemagglutinin agglutinates red blood cells, which is the basis of a diagnostic test called the hemagglutination inhibition test. ✓ hemagglutinin is also the target of neutralizing antibody. Neuraminidase cleaves neuraminic acid (sialic acid) to release progeny virus from the infected cell. -doesdetachment from host cell The hemagglutinin functions at the beginning of infection, whereas the neuraminidase functions at the end. ORTHOMYXOVIRUSES Fusion Competent HA ORTHOMYXOVIRUSES Replication The virus adsorbs to the host cell sialic acid receptors ✓ Enters the cell in vesicles and uncoats within an endosome. ✓ The virion RNA polymerase transcribes the eight genome segments into eight mRNAs in the nucleus. Most of the mRNAs move to the cytoplasm, where they are translated into viral proteins. Some of the viral mRNAs remain in the nucleus, where they serve as the template for the synthesis of the negative-strand RNA genomes for the progeny virions. ✓ The helical ribonucleoprotein assembles in the cytoplasm ✓ Matrix protein mediates the interaction of the nucleocapsid with the envelope ✓ The virion is released from the cell by budding from the outer cell membrane at the site where the hemagglutinin and neuraminidase are located. ORTHOMYXOVIRUSES inside the nucleus -go A Synthesis + SsRNA > - replication ORTHOMYXOVIRUSES Minor antigenic changes are termed antigenic drift. ✓ Antigenic drift is due to the accumulation of point mutations in the gene, resulting in amino acid changes in the - protein. Major antigenic changes, called antigenic shift, domain which gene is a change based on the reassortment of segments of the shifted genome RNA, result in the appearance of a new subtype. big diversity > - ✓ Antigenic shift is most likely to result in an epidemic ORTHOMYXOVIRUSES The antigenicity of influenza B virus undergoes The ability of influenza A virus to cause epidemics is - antigenic drift but not antigenic shift. Llocal outbreaks dependent on antigenic changes in the hemagglutinin and neuraminidase. ✓ The antigenic changes exhibited by influenza B virus are less dramatic and less frequent ✓ Influenza A virus undergoes both major antigenic than those of influenza A virus. gives spidemia shifts as well as minor antigenic drifts. > - ✓ Antigenic shift variants appear infrequently, whereas drift variants appear virtually every year. ORTHOMYXOVIRUSES History The Name Originates From 18th Century Italy, Disease Thought To Be Due To “Influence” of Stars In 1918 “Spanish Flu” Caused 20 Million Deaths Flu shouldn't be Confused with Cold Cold is due to rhinoviruses, coronaviruses, adenoviruses 20,000-30,000 People die from Flu and Flu related complications in USA every year despite vaccines and anti-viral drugs Pandemics Spanish Flu, 1918 (20 million deaths) Asian Flu, 1956 (60,000 deaths) Hong Kong Flu, 1967 Swine Flu, 2009 ORTHOMYXOVIRUSES The big pandemic of 1918 History ORTHOMYXOVIRUSES Factors that sustain epizootics/epidemics ▪ Antigenic drift ▪ Reassortment and antigenic shift ▪ Short term immunity ▪ Cross species transfer ORTHOMYXOVIRUSES Influenza Spread ✓ From person to person by airborne droplets ✓ By contact with contaminated hands or surfaces After the virus has been inhaled: ✓ the neuraminidase degrades the protective mucus layer, allowing the virus to gain access to the cells of the upper and lower respiratory tract ✓ The infection is limited primarily to this area because the proteases that cleave the hemagglutinin are located in the respiratory tract. Despite systemic symptoms, viremia rarely occurs. ORTHOMYXOVIRUSES Influenza infections cause: ✓ cellular destruction and desquamation of superficial mucosa of the respiratory tract ✓ do not affect the basal layer of epithelium. Complete reparation of cellular damage probably takes up to 1 month. Viral damage to the respiratory tract epithelium lowers its resistance to secondary bacterial invaders. The bacteria that live in the nose and throat can descend to the lungs and cause bacterial pneumonia. People over 50, infants, those with suppressed immune function or chronic diseases are most at risk ORTHOMYXOVIRUSES The incubation period from exposure to virus and the onset of illness varies from 1 day to 4 days ✓ depending upon the size of the viral dose and the immune status of the host. Symptoms usually appear abruptly and include: chills, headache, dry cough, follow closely by high fever, generalized muscular aches, malaise, anorexia. The fever usually lasts 3–5 days. - Respiratory symptoms typically last another 3–4 days. - The cough and weakness may persist for 2–4 weeks after major symptoms subside. - ORTHOMYXOVIRUSES These symptoms may be induced by any strain of influenza A or B. Influenza C rarely causes the influenza syndrome, causing instead a common cold illness. Viral shedding ✓ starts the day preceding onset of symptoms, ✓ peaks within 24 hours, - ✓ remains elevated for 1–2 days, ✓ and then declines over the next 5 days. Pneumonia complicating influenza infections can be viral, secondary bacterial, or a combination of the two. ORTHOMYXOVIRUSES Complications in children: Studies show a link between the development of Reye’s syndrome and the use of aspirin for relieving fevers caused by the influenza virus. - ↳ adds N risk Of Reye's Reye’s syndrome ! extremely rare but serious illness that can affect the brain and liver, - occurs most commonly in kids recovering from a viral infection. The disease involves the CNS and the liver children exhibit symptoms of drowsiness, persistent vomiting and change in personality. ORTHOMYXOVIRUSES DIAGNOSIS Rapid influenza tests - provide results in 24 hours - ✓ These tests are 70% accurate for determining if the patient has been infected with the influenza virus and 90% accurate for determining the type of influenza pathogen. Viral cultures - results are available within 3 to 10 days ✓ performed from nasopharyngeal or throat swabs, nasal wash, or nasal aspirates. Serum samples ✓ Blood samples can be tested for the presence of influenza antibody to diagnose recent infection. ORTHOMYXOVIRUSES Depends mainly on secretory IgA in the respiratory tract. IMMUNITY IgG is also produced but is less protective. -not gunna last Cytotoxic T cells also play a protective role. Drugs that are effective against influenza A viruses: amantadine and rimantadine. Drugs that are effective against influenza A viruses and influenza B viruses: TREATMENT zanamivir and oseltamivir. ✓ They are members of a class of drugs called neuraminidase inhibitors, which act by inhibiting the release of virus from infected cells. ORTHOMYXOVIRUSES /Tamivir ↓ blocks neuramidate > - virus cannot detach A replicate ↑ - blocked not able to uncoat > - no replication ORTHOMYXOVIRUSES PREVENTION Existing vaccines are continually being rendered obsolete as the viruses undergo antigenic drift and shift. Inactivated influenza A and B virus vaccines are licensed for parenteral use in humans. The vaccine is usually a cocktail containing one or two type A viruses and a type B virus of the strains isolated in the previous winter’s outbreaks. killed vaccine containing purified protein subunits of the virus #mostly used children , immunocompromised , elderly , health can professionals live vaccine containing temperature-sensitive mutants of influenza A and B viruses. Vaccine May Be Effective For One Year But Not Next Year & & influenza ~ Rhinovious/coronavius