RNA Enveloped Viruses PDF

RNA Enveloped Viruses BY Dr. Nadia Mohammed Ben Zahia  RNA Enveloped ORTHOMYXOVIRUSES CORONAVIRUSES Viruses Influenza Viruses PARAMYXOVIRUSES RHABDOVIRUSES Coronavirus Measles Virus Rabies Virus Mumps Virus...

RNA Enveloped Viruses BY Dr. Nadia Mohammed Ben Zahia  RNA Enveloped ORTHOMYXOVIRUSES CORONAVIRUSES Viruses Influenza Viruses PARAMYXOVIRUSES RHABDOVIRUSES Coronavirus Measles Virus Rabies Virus Mumps Virus RETROVIRUSES Respiratory Syncytial Virus human immunodeficiency viruses Parainfluenza Viruses FILOVIRUSES TOGAVIRUSES Ebola Virus Rubella Marburg Virus Other Togaviruses ARENAVIRUSES FLAFIVIRUS BUNYAVIRUSE  ORTHOMYXOVIRUSES  They are important human pathogens because they cause both outbreaks and epidemic that sicken and kill thousands of people each year.  term myxo refers to the observation that these viruses interact with mucins (glycoproteins on the surface of cells).  Influenza virions are spherical, enveloped particles  ORTHOMYXOVIRUSES  Two types of spikes project from the surface: 1. HN proteins hemagglutinin (H protein) to bind to the cell, neuraminidase(N protein) to initiate infection of the cell. 2. The M (matrix) proteins underlie the viral lipid membrane.  Each nucleocapsid segment contains four proteins (NP, the major nucleocapsid protein, and three P proteins that are present in much  ORTHOMYXOVIRUSES  The virion contains an RNA-dependent RNA polymerase, which transcribes the negative-polarity genome into mRNA.  Influenza virus RNA synthesis and replication occur in the nucleus of the host cell, unlike most other RNA viruses, which replicate in the cytoplasm. The retroviruses also are an exception to this generalization.  Paramyxoviruses belong to Baltimore Group V  Influenza viruses are classified as types A,B, and C  Only the type A viruses are broken down into subtypes, depended on H and N proteins. (14 H and 9 N subtypes).  influenza viruses have both group-specific and type specific antigens. 1. Group-Specific Antigens: including internal nucleoprotein (NP) and matrix protein (M). are common to all influenza viruses, they help the immune system recognize that the virus is a member of the influenza family. 2. Type-Specific Antigens: including surface proteins the Hemagglutinin (H) and the neuraminidase (N), use to differentiate between the three types of influenza viruses A, B, or C. and subtypes e.g. H1N1 & H3N2  Antibody against the hemagglutinin neutralizes the infectivity of the virus (and prevents disease)  Antibody against the neuraminidase does not neutralize infectivity but does reduce disease by decreasing the amount of virus released from the infected cell and thus reducing spread of the virus to adjacent cells  whereas antibody against the group-specific antigen (which is located internally) does not. because these antigens are not accessible to the immune system at the critical stages of  There are two types of antigenic H5N1 H3N2 variation (changes):  (1)antigenic shift: which is a major change based on the re- assortment of segments of the genome RNA  (2) Antigen drift: which is a minor change based on mutations in RNA genome.  Influenza A virus causes worldwide epidemics (pandemics), influenza B virus causes major outbreaks and influenza C virus causes mild  Pathogenesis of Influenza Incubation period is short (1–3 days). Influenza viruses enter the body through inhalation The lRT (tracheobronchial tree) is the primary site of infection. The virus attaches to sialic acid receptors on epithelial cells via HA protein. Neuraminidase protein acts on N-acetyl neuraminic acid in mucus results in liquefaction of mucus, which acts along with mucociliary to spread the virus through the RT. Infected mucosal cells leads to shedding of superficial mucosa. This results in edema (swelling) and infiltration of mononuclear cells, causing symptoms like sore throat, nonproductive cough, and nasal discharge. Systemic Symptoms: The most prominent symptoms are systemic: fever, muscle pain, and extreme fatigue. Influenza remains localized to the respiratory tract, so viremia does not occur.  Laboratory diagnosis Rapid diagnostic test 5. Hospitalization may be necessary Serodiagnosis for severe cases Reverse Transcriptase-PCR  Immunity  Treatment IgA in the respiratory tract is 1. mild to moderate influenza, the main protection. supportive management IgG provides less protection. 2. Amantadine and rimantadine are Cytotoxic T cells play a protective effective against influenza A virus role against the virus 3. neuraminidase inhibitors: Zanamivir  Transmission and oseltamivir (Tamiflu) are antiviral respiratory droplets agents effective against influenza A,B  Prevention 4. Peramivir (Rapivab) is administered Chemoprophylaxis by IV and became available in 2015. against both influenza A and B neuraminidase inhibitors annual flu vaccine Paramyxoviruses  They are spherical viruses, have helical nucleocapsid, surrounded by an envelope contains a non segmented, negative-strand RNA genome.  envelope contains two types of proteins. 1.The HN protein (Hemagglutinin, Neuraminidase) helps binding of the virus to a cell ” measles virus lacks the neuraminidase activity” while Respiratory Syncytial Virus lacks the both. 2. The F protein (fusion), helps virus fuse to cellular membranes, thus facilitating virus entry.  Paramyxoviridae  They differ from orthomyxoviruses in that their genomes are not segmented, they have a larger diameter, and their surface spikes are different.  The virion contains an RNA-dependent RNA polymerase, which transcribes the negative-polarity genome into mRNA  Paramyxoviridae family subdivided into two subfamilies. 1. Paramyxovirinae subfamily has three genera include: 1) Paramyxovirus (parainfluenza viruses, which cause URT infections). 2) Rubulavirus (mumps virus). 3) Morbillivirus (measles virus). 2. Pneumovirinae subfamily, which includes respiratory syncytial virus, a major respiratory tract pathogen in the pediatric population  1.Paramyxovirus (Parainfluenza viruses)  The term “parainfluenza” was first coined because infected individuals may present with influenza- like symptoms, and, like influenza virus, these viruses have  The H and N proteins are on the same spike.  the F protein is on a separate spike.  Negative sense, single stranded RNA genome  There are four types, which are distinguished by antigenicity, cytopathic effect, and pathogenicity.  The clinically important viruses in this genus are type 1 and type 2 responsible for croup, type 3 Bronchiolitis and pneumonia, especially in young children and infants. type 4 Mild respiratory infections.  Clinical Findings Parainfluenza viruses are the main cause of croup in children younger than 5 years of age. Which characterized by a harsh cough and hoarseness. Also cause a variety of respiratory diseases such as the common cold, pharyngitis, laryngitis, otitis media, bronchitis, and pneumonia.  Pathogenesis & Immunity Virus attachment using its hemagglutinin protein. enters cells by fusion with the cell membrane using its F protein. virus replicates rapidly in the cytoplasm causing inflammation in the respiratory tract and high levels of inflammatory cytokines are released (7-10 days after exposure).appear as inflammation, necrosis, sloughing of respiratory epithelium, edema, and excessive mucus production.  Immunity  Cell Mediated Immunity  Humoral Immunity (Antibodies against HN and F) Neutralizing antibodies are present in most infants at birth but decline after 6 M Secretory IgA antibodies play a significant role in defense.  Immunity to HPIV is Long-lasting Immunity but reinfections can occur due to the presence of multiple serotypes of HPIV  Laboratory Diagnosis Treatment & Prevention Direct antigen detection no antiviral therapy or a vaccine Serodiagnosis available. RT-PCR managing symptoms and providing  Transmission supportive care respiratory droplets Hand hygiene and avoiding contact with infected individuals  Rubulavirus (mumps virus).2  helical nucleocapsid contains one piece of negative, single-stranded RNA  Virion has RNA polymerase  The virion has two types of envelope spikes : one with both hemagglutinin and neuraminidase activities and the other with cell-fusing and hemolytic activities  The virus has a single serotype.  Neutralizing antibody is directed against the hemagglutinin.  Humans are the natural host  It has an internal nucleocapsid soluble (S) antigen  Pathogenesis  The incubation period is long 12 to 25 days  The initial site of infection is the upper respiratory tract.  The virus spreads to local lymph nodes and then via the bloodstream to other organs, especially the parotid glands, testes, ovaries, meninges, and pancreas.  Fever, headache, and earache are the initial symptoms. These symptoms are followed by painful swelling of the parotid gland. Initially, it may be unilateral but may become bilateral later. The condition is accompanied by fever, local pain, and tenderness. Epididymo-orchitis is the second most common manifestation in adults, which is usually preceded by parotitis. Orchitis may occasionally cause testicular atrophy and sterility.  Immunity Cell-mediated immunity (CMI) Humoral immunity Antibodies against the soluble S antigen and antibodies against hemagglutinin provide lifelong immunity to mumps.  Laboratory Diagnosis The virus can be isolated in cell culture and detected by hemadsorption. Serodiagnosis. PCR.  Treatment No antiviral therapy is available.  Prevention Vaccine  Morbillivirus (Measles Virus)  Measles (Rubeola) is one of the five classic exanthematous diseases of the childhood; others being Chickenpox (Varicella), Rubella (German Measles), Roseola (sixth disease) and fifth disease.  Measles virus is spherical, but is often pleomorphic.  It contains a negative-sense, single stranded RNA genome.  The helical nucleocapsid is surrounded by an envelope  The envelope carrying H and F protein on its surface.  RNA polymerase in virion.  It has a single serotype.  Pathogenesis incubation period 10 to 14 days The virus initiates infection and replicates locally in the trachea and bronchial epithelial cells of the RT. Virus spreads to local lymph nodes and then systemically in lymphocytes, perhaps carried by pulmonary macrophages, via the blood to other organs, including the skin. conjunctiva, RT, UR, lymphatic system, blood vessels, and the CNS  Clinical finding: Causing Fever, Dry cough, coryza, conjunctivitis, Koplik's spots and skin rash start at hair line then spread.  The characteristic rash seen in measles is caused primarily by cytotoxic T cells attacking the measles virus-infected epithelial cells in the skin.  Immunity Cell-mediated immunity (CMI) antibodies provide limited protection against measles due to cell-to-cell  Treatment virus spread. No antiviral therapy is available. maternal antibodies provide protection for infants during the first  Prevention 6 months. Vaccine combination with mumps and Lifelong immunity by memory T rubella (MMR) vaccines. cells and memory B cells  Laboratory Diagnosis The virus is rarely isolated. Serologic tests are used if necessary. PCR assay is available.  4.Respiratory Syncytial Virus  Most important cause of bronchiolitis and pneumonia in infants. Also causes otitis media in older children.  Enveloped virus with a helical nucleocapsid  one piece of negative sense, single-stranded RNA.  It has RNA polymerase.  Unlike other paramyxoviruses it has only a fusion (F) protein on its surface spike  The F protein induces the fusion of the infected cells with adjoining cells, resulting in the formation of large multinucleated syncytia.  It has two serotypes  each serotype has multiple subtypes  Pathogenesis The virus initiates infection in the epithelial cells of URT. Spread to the lower respiratory tract by cell to cell spread, resulting in pneumonia. The virus usually does not cause any viremia or systemic spread. The virus causes necrosis of the small airway epithelium, plugging of the lumens with exudates, and edema, leading to obstruction of the normal airways of the young infants.  Immunity Cell-mediated immunity (CMI) antibodies provide limited protection due to cell-to-cell virus spread. maternal antibodies is not protect infants. Natural infection by RSV does not prevent reinfection by the virus.  Laboratory Diagnosis Direct antigen detection Serodiagnosis  Transmission Respiratory droplets  Treatment Aerosolized ribavirin for very sick infants.  Prevention Passive immunization with anti-RSV immunoglobulins in high-risk infants. Handwashing and the use of gloves may prevent nosocomial outbreaks in the newborn nursery.  TOGAVIRUSES  There are two major groups of human pathogens: 1. The alphavirus group: includes eastern & western encephalitis viruses 2. The rubivirus group: consists only of rubella virus.  TOGAVIRUSES RUBELLA VIRUS German measles one piece of positive sense, single-stranded RNA. an icosahedral nucleocapsid. has no virion polymerase. It has three structural proteins, capsid (C) protein encloses the viral RNA, forming the nucleocapsid; the two other proteins (E1 and E2) are glycoproteins that form the hemagglutinin-containing viral spikes. The virus has a single antigenic type (serotype). Humans are the natural host. This virus causes rubella and congenital rubella syndrome. Congenital rubella syndrome is characterized by congenital malformations.  diseases Rubella Rubella is a milder, shorter disease than measles. incubation period of 14 to 21 days. initially headache, low fever, coryza, sore throat and forchheimer spots, a maculopapular rash, which starts on the face and progresses downward to extremities typically lasts 3 days. Posterior auricular lymphadenopathy is characteristic. When rubella occurs in adults, especially women polyarthritis Congenital Rubella Syndrome Occur when a nonimmune pregnant woman is infected during the first trimester, especially the first month involve primarily the heart, the eyes, and the brain.  Pathogenesis Initial replication in the nasopharynx and local lymph nodes. spreads via the blood to the internal organs and skin. The origin of the rash is unclear.  Transmission Respiratory droplets  Immunity Vertical transmission Natural infection leads to lifelong immunity. Second cases of rubella do not occur.  Treatment There is no antiviral therapy  Laboratory Diagnosis  Prevention Serodiagnosis vaccination immunoglobulins.  FLAVIVIRUSES they have an icosahedral nucleocapsid single-stranded, positive-polarity RNA genome The genus Flavivirus is composed of more than 60 virus. such as yellow fever virus St. Louis encephalitis virus Japanese encephalitis virus dengue fever virus West Nile virus all of which are mosquito-transmitted. Tick-borne encephalitis virus by ticks. All Flaviviruses are serologically related.(share a common group antigen)  BUNYAVIRUSES The name comes from the Bunyamwera River in Uganda They are large, spherical with helical nucleocapsid. They have a triple-segmented and a single-stranded RNA.  They includes more than 150 members including 1. La Crosse virus 2. California encephalitis virus 3. Chittor virus. These three viruses are related antigenically and produce similar clinical diseases. These viral infections are transmitted by mosquitoes. No specific antiviral therapy is available for Bunyavirus infection.  CORONAVIRUSES named for the crown-like appearance of their virions on electron microscopy. These viruses are the second most important cause of the common cold. spherical enveloped virion positive, single stranded RNA genome helical nucleocapsid They have 4 structural proteins: Spike (S) Protein S1 subunit: Binding ,S2 subunit: fusion Envelope (E):assembly, budding. Membrane (M):assembly & virus’s shape. Nucleocapsid (N): binding & packaging RNA into new viral particles.  Clinical Syndromes Common cold ◗.Common cold caused by coronaviruses has an incubation period of 3 days.The condition is characterized by rhinorrhea, sore throat, and low-grade fever.The condition typically lasts for several days Gastroenteritis ◗.In children and adults. The symptoms are mild, and the condition is self-limiting SARS ◗ It is a potentially life-threatening infection, it onset as flu-like syndrome, which.progress to pneumonia, respiratory failure, and in some cases death.IP 2 to 7 days, although it maybe as long as 2 weeks ,Flu-like prodrome characterized by fever, fatigue, chills, malaise, anorexia and myalgia,Hypoxia, dry and nonproductive cough, dyspnea, and breathing difficulties are common findings. Chest X ray shows interstitial ground glass infiltrates  Pathogenesis and Immunity Coronavirus 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.  Laboratory Diagnosis antibody-based and PCR-based tests.  Transmission respiratory aerosol.  Treatment & Prevention There is no antiviral therapy. A combination of ribavirin and steroids has been tried in the treatment of life- threatening cases of SARS, but their efficacy is uncertain. Recently vaccination.  RHABDOVIRUSES Rabies Virus It is a bullet-shaped virus with one end rounded or conical and the other end planar or concave. helical nucleocapsid. linear negative-sense, single-stranded RNA genome. RNA-dependent RNA transcriptase. Have M (matrix) protein : group-specific antigen (diagnostic antibodies) G (glycoprotein) proteins: serotype-specific antigen, forming glycoprotein spikes and it is antigenic, (induce virus-neutralizing antibody). Rabies virus possesses hemagglutinating property. Rabies virus has a broad host range.  Disease Rabies virus causes rabies, a viral infection of the central and peripheral nervous systems that causes encephalitis with or without paralysis. It is mostly fatal.  Clinical Findings The prodromal symptoms such as fever, anorexia, and paresthesias at the bite site  Rabies manifests as either of two forms: “furious” (encephalitic) or “dumb” (paralytic). The furious form occurs in about 80% of cases. agitation, delirium, seizures, and hydrophobia occur. The dumb form, these symptoms do not occur. ascending paralysis occurs. Death almost invariably occurs following both forms.  Pathogenesis Incubation period: The average period of incubation is 20–90 days. The virus multiplies locally at the bite site, infects the sensory neurons, and moves to CNS and multiplies in it. then travels down the peripheral nerves to the salivary glands and other organs. From the salivary glands, it enters the saliva to be transmitted by the bite. There is no viremic stage. Within the central nervous system, encephalitis develops, with the death of neurons and demyelination. Infected neurons contain a Negri body, which is important in laboratory diagnosis.  Laboratory finding PCR Assay: Detects viral genetic material from saliva, spinal fluid, or brain tissue Fluorescent Antibody Staining: Applied to a skin biopsy (usually from the neck near the hairline). Virus Isolation: From saliva, spinal fluid, or brain tissue. Antibody Titer Rise: A rise in antibody levels over time can indicate infection. Negri Bodies: Seen in corneal scrapings or autopsy specimens.  Transmission bite of wild animals  Treatment There is no antiviral drug. Only supportive treatment is available.  Prevention preexposure with rabies vaccine and postexposure immunization with rabies vaccine and human rabies immune globulin  RETROVIRUSES Retroviruses are enveloped, spherical viruses. Single-stranded RNA genome, typically with two identical copies of RNA. the RNA-dependent DNA polymerase (reverse transcriptase), giving the virus its name. Integrase integrates the proviral DNA into the host cell’s genome (integration). Protease Cleaves viral polyproteins. RNA Polymerase II (Host) Transcribes the integrated proviral DNA into viral mRNA for protein synthesis and RNA genome replication.  RETROVIRUSES All oncogenic RNA viruses are classified in the family Retroviridae; but NOT all retroviruses are oncogenic. classified into three subfamilies: Oncovirinae, Lentivirinae (HIV), Spumavirinae  Human Immunodeficiency Virus The HIV RNA genome contains three major genes: The gag gene codes for CA, MA, and NC (core and matrix proteins). The pol gene that codes for reverse transcriptase, protease, integrase, ribonuclease. The env gene that codes for TM and SU (transmembrane and surface proteins).  Pathogenesis It results from either tissue destruction by the virus itself or the host’s response to virus-infected cells HIV can induce state that leads to opportunistic diseases that are rare in the absence of HIV infection.  Development from HIV infection to end-stage AIDS progresses through several phases 1.Initial Infection: HIV infects macrophages in the genital tract, spreads to lymphoid tissue, and infects CD4+ cells. 2. Acute Phase: 2-3 weeks post-infection, flu-like symptoms occur, with high virus replication and seroconversion. 3. Latent Period: HIV remains dormant in most cells, with occasional viral peaks; immune function controls virus spread but CD4+ count declines slowly. 4. Clinical Complications: Symptoms like swollen lymph nodes, diarrhea, and opportunistic infections appear, but CD4+ count stays above 200/μl. 5. Progression to AIDS: HIV replication increases, immune evasion occurs, and CD4+ cells are lost, leading to AIDS. 6. End-stage AIDS: Severe immune failure leads to opportunistic infections and malignancies  Laboratory Diagnosis HIV Antibody Tests: ELISA, rapid HIV Tests HIV Antigen Tests : HIV p24 Antigen Test: Detects the p24 protein, which appears early in infection, before antibodies are formed. HIV Nucleic Acid Tests (NAT): Detects the presence of HIV RNA. Western Blot Test: Confirms HIV infection after a positive antibody test.  Transmission  prevention Sexual transmission health education. blood transfusion screening of blood and blood products. Parenteral transmission infection control. Vertical transmission  Treatment Multiple-Drug Therapy: combination of drugs targeting different steps in the HIV replication cycle reduces Highly Active Antiretroviral Therapy (HAART): A combination of three drugs that lower viral load and increase CD4+ count HIV persists in "sanctuaries" like the CNS and lymphoid reservoirs. Nucleoside/nucleotide analog reverse transcriptase inhibitors (NRTIs): Block viral DNA synthesis (e.g. lamivudine). Non-nucleoside reverse transcriptase inhibitors (NNRTIs): Bind to reverse transcriptase and prevent its function (e.g., efavirenz, nevirapine). Protease inhibitors (PIs): Prevent maturation of the virus (e.g., ritonavir, saquinavir). Viral fusion inhibitor: Enfuvirtide inhibits fusion of HIV with host cell membranes. Perinatal Treatment: Zidovudine during pregnancy reduces the risk of HIV transmission from mother to infant  FILOVIRUSES Filoviruses are long filamentous (filo = thread) viruses. They are the longest viruses, often measuring thousands of nanometers There are two important filoviruses that cause human disease: 1. Ebola virus 2. Marburg virus. EBOLA VIRUS has a single-stranded, nonsegmented, negative polarity RNA genome. has an RNA-dependent RNA polymerase in the virion. The nucleocapsid has helical symmetry. The surface proteins of Ebola virus are antigenically distinct from those of Marburg virus. Ebola virus is one of the most virulent human viruses. Ebola virus causes Ebola hemorrhagic fever (EHF).  Clinical Findings The incubation period is typically 5 to 7 days but may be up to 21 days. EHF begins with fever, headache, sore throat, myalgia, arthralgia, epigastric pain, vomiting, and diarrhea. Later, bleeding into the skin and gastrointestinal tract occurs, followed by shock and disseminated intravascular coagulation leading to multiorgan failure.  The hemorrhages are the result of both severe thrombocytopenia and death of endothelial cells. Marked lymphopenia occurs.  Pathogenesis & Immunity The high mortality rate of Ebola virus is attributed to several viral virulence factors: I glycoprotein kills endothelial cells, resulting in hemorrhage. two other proteins inhibit the induction and action of interferon. Lymphocytes, Macrophages. dendritic cells are killed. Hepatocytes are also killed leading to liver failure. The antibody response is often ineffective in preventing disease. The mortality rate associated with this virus can be up to 90%. In some patients who recover from EHF, a post-Ebola syndrome (PES) occurs. The findings in PES include eye pain, blurred vision, hearing loss, headache, joint pain, fatigue, and insomnia. In one patient with uveitis, infectious Ebola virus was recovered from fluid aspirated from the interior of his eye several months after recovery  Laboratory Diagnosis ELISA PCR  Transmission The vector responsible for transmission of Ebola virus is not known, but infected primates appear to be responsible.  Treatment & Prevention No antiviral therapy is available. Supportive therapy immune serum globulins the wearing of personal protective equipment Quarantine of individuals thought to be exposed for 21 days There is no vaccine ARENAVIRUSES The name arena means sand that refers to granules at the surface of the virion that are nonfunctional ribosomes. Arenaviruses are the pleomorphic, enveloped viruses The genome is two circles negative-sense RNA S (small segment (and L (large segment).  Clinical Syndromes Lymphocytic choriomeningitis Lassa fever South American hemorrhagic fever  Pathogenesis and Immunity Arenaviruses primarily infect macrophages and cause the vascular damage. Pathogenesis of arenaviruses infection is mainly by T-cell-mediated immune responses. which play a significant role in worsening tissue.  Transmission  Laboratory Diagnosis the natural reservoir for these viruses is Serodiagnosis unknown. they can be transmitted to humans from infected  Treatment monkeys and probably other animals or by Ribavirin exposure to infected blood or other body fluids.  Prevention Depends on the rodent control measures and avoidance of high-density rodent-infested areas. No vaccines are available thank you