RNA-viruses-2.pdf

MLS 13A: Mycology and Virology RNA VIRUSES 2nd SEMESTER | S.Y 2023 - 2024 ARENAVIRUS MEDICALLY IMPORTANT RNA VIRUSES...

MLS 13A: Mycology and Virology RNA VIRUSES 2nd SEMESTER | S.Y 2023 - 2024 ARENAVIRUS MEDICALLY IMPORTANT RNA VIRUSES FAMILY: Arenaviridae VIRION: enveloped with large peplomers, RNA Viruses that Cause Serious Diseases in Humans irregular capsid Family Viral Members GENOME: segmented, 2 segments (L,S), (-) sense, ssRNA Arenaviridae Lymphocytic choriomeningitis virus, Lassa fever virus MULTIPLICATION: RA (CYTOPLASM); M (CM) EXIT: buds from cell membrane Astroviridae Gastroenteritis-causing astroviruses INFECTS: Endothelial cells Bunyaviridae Arbovirus, including California encephalitis and Lacrosse viruses; MOT: urine or saliva of rats, direct contact nonarbovirus, including sin nombre, and related hantaviruses (human to human), inhalation of aerosols. Caliciviridae Norovirus and hepatitis E virus DISEASES Old World Hemorrhagic Fever - Lassa complex Coronaviridae Coronaviruses, including SARS coronavirus fever virus Filoviridae Ebola and Marburg hemorrhagic fever viruses New World Hemorrhagic Fever - Tacaribe complex fever virus Lymphocytic choriomeningitis (LCM) Flaviviridae Arboviruses, including yellow fever, dengue, West Nile, Japanese Junin H fever - Argentina encephalitis, and St. Louis encephalitis viruses; nonarboviruses, Machupo H fever - Bolivia including Hepatitis C virus Guanarito H fever - Venezuela Sabia H fever - Brazil Orthomyxoviridae Influenza A, B, and C virus Whitewater Arroyo H fever - USA DIAGNOSIS Paramyxoviridae Parainfluenza viruses, mumps virus, measles virus, RSV, metapneumovirus, Nipah virus RT-PCR, Serology Requires maximum containment conditions in the laboratory Picornaviridae Polio virus, coxsackie A viruses, coxsackie B viruses, echoviruses, enteroviruses 68-71, enterovirus 72 (hepatitis A virus), rhinoviruses ASTROVIRUS FAMILY: Astroviridae Reoviridae Rotavirus spp., Colorado tick fever virus VIRION: star-shaped outline on their surface Retroviridae HIV types 1 and 2, HTLV types 1 and 2 GENOME: linear, (+) sense, ssRNA Associated with gastroenteritis in humans and animals Rhabdoviridae Rabies virus Similar in size to picornaviruses Togaviridae Eastern, Western, and Venezuela equine encephalitis viruses, rubella virus Note: HIV - human immunodeficiency virus; HTLV - human T-lymphotropic viruses; RSV - respiratory syncytial virus; SARS - severe acute respiratory syndrome MLS 3C YONGQUE  MLS 13A: Mycology and Virology RNA VIRUSES 2nd SEMESTER | S.Y 2023 - 2024 DISEASES BUNYAVIRUS (ARBO-GROUP) Hantavirus - Korean H fever, Hemorrhagic fever with renal syndrome (HFRS), Seoul virus FAMILY: Bunyaviridae Sin Nombre virus - causes Hantavirus Pulmonary Syndrome (HPS) ARBOvirus - California encephalitis group DIAGNOSIS (containing La Crosse virus) Serology, Antibody detection in CSF, RT-PCR Non-ARBO - rodent borne Hantavirus group (containing sin nombre virus) CALICIVIRUS VIRION: enveloped, helical, spherical or pleomorphic capsid FAMILY: Caliciviridae GENOME: segmented, 3 segments (S, M, L), (-) VIRION: naked, icosahedral sense or ambisense, ssRNA Similar to Picornavirus but has spikes and MULTIPLICATION: R (CYTOPLASM); AM cup-like calyx depressions (ER/GOLGI COMPLEX) Resembles “star of David appearance” EXIT: buds from the Golgi complex, released by GENOME: nonsegmented, (+) sense, ssRNA fusion of vesicle with cell membrane not by MULTIPLICATION: RA (CYTOPLASM) budding EXIT: cell lysis INFECTS: Endothelial cells INFECTS: Epithelial lining of the GI tract MOT: arthropod insects, aerosolized rodent MOT: fecal - oral route feces for Hantaviruses DISEASES DISEASES Norwalk (Norovirus) - nausea, vomiting, watery diarrhea with no blood nor mucus La Crosse encephalitis - Aedes triserius in older children and adults Crimean - Congo H fever - Ixodid ticks Gastroenteritis caused by Caliciviruses are low infectious diseases and are resistant Sandfly fever - Phlebotomus papatasii to drying and chlorine Rift Valley fever - Aedes spp. Nausea, vomiting, and diarrhea Hemorrhagic fevers, Nephropathy DIAGNOSIS Severe pulmonary syndrome Non-cultivable DIAGNOSIS PCR, EIA, EM CSF samples for serological testing CALICIVIRUS (HEPATITIS E) BUNYAVIRUS (NON-ARBO GROUP) FAMILY: Caliciviridae FAMILY: Bunyaviridae VIRION: naked, icosahedral VIRION: enveloped, helical capsid Similar to Picornavirus but has spikes and cup-like calyx depressions GENOME: segmented, 3 segments (S, M, L), (-) sense or ambisense, ssRNA Resembles “star of David appearance” MULTIPLICATION: R (CYTOPLASM); AM (ER/GOLGI COMPLEX) GENOME: non-segmented, (+) sense, ssRNA EXIT: buds from the Golgi complex, released by fusion of vesicle with cell membrane not MULTIPLICATION: RA (CYTOPLASM) by budding EXIT: cell lysis INFECTS: Endothelial cells INFECTS: Epithelial lining of the GI tract MOT: rodent-borne (field mice) MOT: fecal - oral route MLS 3C YONGQUE  MLS 13A: Mycology and Virology RNA VIRUSES 2nd SEMESTER | S.Y 2023 - 2024 DISEASES DISEASES Similar to Hepatitis A - Acute stage only and NO chronicity Water-borne hepatitis - detrimental for pregnant women Common colds DIAGNOSIS SARS-COV (MERS-CoV, COVID-19) - dry Serology non-productive cough, alveolar damage caused by the virus or by cytokines induced by QUICK CHECK! HEPATITIS VIRUSES the virus Virulence factor - has the capacity for high frequency recombination (Deletion mutation) DIAGNOSIS RT-PCR, Antigen-Detection Kits, Antibody Testing CORONAVIRUS FAMILY: Coronaviridae VIRION: enveloped, “pear-shaped” peplomers giving a crown-like appearance Largest RNA virus PATHOPHYSIOLOGY OF COVID-19 Contains S protein (spike) which causes cell fusion and facilitates viral entry to host cells by attaching to specific receptors, N protein (nucleocapsid), and M protein (membrane) for structure and shape Helical or complex capsid symmetry GENOME: non-segmented, (+) sense, ssRNA MULTIPLICATION: R (CYTOPLASM); AM (ER) Envelope comes from ER EXIT: released by fusion in the plasma membrane INFECTS: upper respiratory tract MOT: respiratory droplet MLS 3C YONGQUE  MLS 13A: Mycology and Virology RNA VIRUSES 2nd SEMESTER | S.Y 2023 - 2024 Often associated with bilateral ground-glass opacities on chest imaging FILOVIRUS FAMILY: Filoviridae VIRION: Filamentous, thread-like, enveloped with large peplomers, helical capsid sometimes irregularly shaped GENOME: non-segmented, (-) sense, ssRNA, striated core MULTIPLICATION: RA (CYTOPLASM); M (CM) EXIT: buds from plasma membrane MERS SARS Covid - 19 INFECTS: macrophages, endothelial cells, Virus Species Middle East respiratory hepatocytes Severe acute respiratory MOT: respiratory droplets and body fluids syndrome-related syndrome-related coronavirus Coronavirus (human-to-human) Individuum MERS-CoV SARS-CoV SARS-Cov2 DISEASES Ebola virus - short virus First reported Saudi-Arabia (2012) China (2002) China (2019) Zaire strain - 2 - 21 days incubation Current status No reports since Sudan strain - 2 - 21 days incubation Active Active Reston strain 2004 Marburg virus - long virus with 4-16 days incubation Infections 2521+ 8098 3,500,000+ Cause severe hemorrhagic fever in Africa and Germany respectively Severe hemorrhage and liver necrosis Fatality rate 34% 10% ~1% DIAGNOSIS Cell culture (Primary Monkey Kidney = PMK), Modern molecular techniques, EM Preventive/Curative None None None Requires maximum containment conditions Treatment FLAVIVIRUS FAMILY: Flaviviridae VIRION: spherical, enveloped, icosahedral GENOME: non-segmented, (+) sense, ssRNA Dengue fever has 4 serotypes MULTIPLICATION: R (CYTOPLASM); AM (ER) EXIT: buds from GC and released by fusion of vesicle with plasma membrane not by budding INFECTS: macrophages (Dengue), CNS (Encephalitis), Hepatocytes (HCV & yellow fever) MOT: Aedes aegypti (Dengue), Arthropod bite (Encephalitis), parenteral (HCV), Aedes or Haemagogus spp. MLS 3C YONGQUE  MLS 13A: Mycology and Virology RNA VIRUSES 2nd SEMESTER | S.Y 2023 - 2024 DISEASES ORTHOMYXOVIRUS Dengue fever - malaise, chills, headache, joint pains, “breakbone fever” FAMILY: Orthomyxoviridae Dengue hemorrhagic fever - thrombocytopenia, prolonged bleeding time VIRION: spherical, helical capsid, enveloped, HA and NA spikes Dengue shock syndrome - more deadly, hemoconcentration shock GENOME: segmented, 8 linear segments, (-) sense, ssRNA St. Louis Encephalitis, Japanese Equine Encephalitis- characterized by “flaccid HA - hemagglutinin activity (binds to host receptor) paralysis” NA - neuraminidase activity (fuses with host’s cell membranes) Hepatitis C - Non-A, Non-B (NANB) hepatitis, maybe oncogenic MULTIPLICATION: RA (NUCLEUS); M (CM) Jungle fever - monkeys, treetop mosquitos, Haemagogus spp., Africa, South EXIT: buds from plasma membrane America INFECTS: epithelial cells of the respiratory tract Urban yellow fever - humans, Aedes aegypti, sudden onset of fever, upper GI MOT: respiratory droplet hemorrhage with hematemesis - “black vomit”, has not invaded Asia LATENCY: Birds have become the reservoir of all human influenza viruses. DIAGNOSIS Serology Orthomyxoviridae (influenza viruses) are a major determinant of the morbidity and RT-PC mortality caused by respiratory disease, and outbreaks of infection sometimes occur in worldwide epidemics. *Arthropod-borne viruses (arboviruses) are taxonomically Influenza has been responsible for millions of deaths worldwide. heterogeneous but were once grouped together because of their common mode of transmission. Viruses adapted to arthropod vectors occur in several taxonomic families, including the Togaviridae, Mutability and high frequency of genetic reassortment and resultant antigenic Flaviviridae, and Bunyaviri- changes in the viral surface glycoproteins make influenza viruses formidable dae. The virus group within Togaviridae that includes arboviruses is the challenges for control efforts. alphavirus group. Common arboviruses are referred to as bunyaviruses, flaviviruses, and alphaviruses. Influenza viruses (orthomyxoviruses) are divided into three types; A, B, and C, based on antigenic differences in their ribonucleoprotein (NP) and matrix (M) protein antigens. Influenza A virus has the greatest virulence and predominance in epidemic spreads because of their ability to undergo genetic changes and existence in several species. MLS 3C YONGQUE  MLS 13A: Mycology and Virology RNA VIRUSES 2nd SEMESTER | S.Y 2023 - 2024 ANTIGENIC DRIFT VS. ANTIGENIC SHIFT DIAGNOSIS Cell culture (PMK), Serology DRIFT SHIFT Hemadsorption (due to HA) Minor change within subtype Major change, new subtype Point mutations Exchange of gene segments Occurs in A and B subtypes Occurs in subtypes A only May cause epidemics May cause pandemics Example: A/Fujian (H3N2) replaced A/ Example: H3N2 replaced H2N2 in 1968 Panama (H3N2) in 2003-2004 IMPORTANCE OF HEMAGGLUTININ Hemagglutinins attach to N-acetylneuraminic (sialic) acid-only containing glycoprotein or glycolipid receptor sites on human respiratory cell surfaces, which is a critical first step in initiating infection of the cell. IMPORTANCE OF NEURAMINIDASE Neuraminidase promotes a smooth passage for the virus in the respiratory tract by inactivating mucoprotein receptors in respiratory secretions. It also destroys viral receptors, thus preventing aggregation and superinfection in infected cells. DISEASES Human influenza (Type A, B, and C) Primary influenza pneumonia Croup, Otitis media UNDERSTANDING THE NAMING OF FLU VIRUSES ANTIGENIC SHIFT - Drastic reassortment, every 10-40 years, leads to a pandemic ANTIGENIC DRIFT - Mild reassortment, accumulated point mutations lead to formation of new strain ○ Type A - every 2-3 years ○ Type B - every 3-6 years, leads to an epidemic Avian influenza, Swine influenza, Equine influenza Examples of Influenza Epidemics and Pandemics ○ H1N1 (swine origin) - Spanish flu (1918-1919) where more than 20M died from complications with bacterial pneumonia; Russian flu ○ H2N2 - Asian flu (1957) ○ H3N2 (human origin) - Hong Kong flu (1968) ○ H2N8 - 1890 epidemic ○ H3N8 (avian origin) - 1900 epidemic MLS 3C YONGQUE  MLS 13A: Mycology and Virology RNA VIRUSES 2nd SEMESTER | S.Y 2023 - 2024 PARAMYXOVIRUS PICORNAVIRUS FAMILY: Paramoxyviridae FAMILY: Picornaviridae VIRION: spherical, helical capsid, enveloped, HA, NA spikes Coxsackie virus - enterovirus from New York GENOME: non-segmented, linear, (-) sense, ssRNA HAV - enterovirus causing hepatitis MULTIPLICATION: RA (CYTOPLASM); M (CM) Poliovirus, Rhinovirus EXIT: buds from the plasma membrane VIRION: naked, icosahedral capsid INFECTS: epithelial cells of the respiratory tract GENOME: non-segmented, linear, (+) sense, ssRNA MOT: respiratory droplets MULTIPLICATION: RAM (CYTOPLASM) LATENCY: NONE Poliovirus DOES NOT MULTIPLY IN THE MUSCLES DISEASES EXIT: cell lysis Adults - upper respiratory tract infection (URTI), rarely pneumonia INFECTS: Children - URTI, croup, bronchiolitis, pneumonia ○ Coxsackie - oropharynx, GIT, heart, pleura Croup - a disease that causes swelling of the airways and problems breathing. Children with croup often ○ HAV - Peyer’s patches, liver, small intestine have a high-pitched “creaking” or whistling sound when breathing in (stridor). ○ Poliovirus and Rhinovirus - oropharynx, GIT, neck LN, CNS DIAGNOSIS MOT: respiratory droplets, fecal-oral Cell culture (PMK), Serology DISEASES Hemadsorption (due to HA) Group A Coxsackie - Herpangina (papules in oropharyngeal area) Group B Coxsackie - Pleurodynia (inflammation of the intercostal muscles) Infectious myocarditis and pericarditis HAV - Acute hepatitis, never becomes chronic, no carrier state, low mortality Poliovirus - Poliomyelitis, Infantile paralysis, Flaccid paralysis, Respiratory paralysis Rhinovirus - Rhinitis, runny nose, common cold DIAGNOSIS Cell culture (PMK), Nucleic acid assays, PCR Serology techniques MLS 3C YONGQUE  MLS 13A: Mycology and Virology RNA VIRUSES 2nd SEMESTER | S.Y 2023 - 2024 REOVIRUS LIFE CYCLE FAMILY: Reoviridae Contain an RNA-dependent DNA polymerase (reverse Rotavirus - does not produce a disease at the site transcriptase) for replication. which it was recovered Reverse transcriptase uses viral RNA as a template to VIRION: naked, icosahedral capsid make dsDNA that then moves into the nucleus where GENOME: segmented, 10 -12 segments, linear, it is integrated into the host chromosome. This stage is ambi-sense, dsRNA, “wheel-like structure” called Provirus. MULTIPLICATION: R (CYTOPLASM); AM (ER) The genome is transcribed into mRNA by host RNA EXIT: cell lysis polymerase. INFECTS: Epithelial cells of the GI tract MOT: fecal-oral DISEASES RETROVIRUS: LENTIVIRUS Infantile gastroenteritis - ages 6 months - 2 years old, in cold winter cases, Human immunodeficiency virus 1 (HIV-1) and HIV-2 are members of this genus. blood-streaked stool HIV is the causative agent of AIDS. HIV-1 causes a more severe infection and is DIAGNOSIS more prevalent than HIV-2. Serology techniques (EIA, Latex Agglutination) Spread of the virus is through sexual contact, IV drug use, congenital transmission or through contaminated blood products. RETROVIRUS (HIV) FAMILY: Retroviridae Initially affects macrophages and dendritic cells, then the host’s CD4+ T cells ○ SUBFAMILY: Lentivirinae ○ These cells are key to both humoral-mediated and cell-mediated immune VIRION: spherical, enveloped, helical nucleoprotein, icosahedral, 80-130nm responses. GENOME: linear, non-segmented, (+) sense, ssRNA, diploid (presence of DNA and ○ As more T cells are destroyed, immune function deteriorates RNA) ○ CD4 is the primary receptor for the virus. Gp 120 binds to CD4 molecule of the host cell ○ CXCR 4 and CCR5 are important co-receptors MULTIPLICATION: R (NUCLEUS) wherein RNA is transcribed to DNA; AM (CYTOPLASM) Acute infections - often mild, rarely diagnosed and resembles IM. EXIT: buds from the plasma membrane Virus replication occurs at a high rate in lymphoid tissue but the patient remains INFECTS: CD4+ cells asymptomatic for many years. MOT: sexual, parenteral The host is able to replace infected T cells faster than they are destroyed. The condition is referred to as “clinical latency”. Eventually, the virus begins to destroy T cells faster than they can be replaced. Since the patient is now immunocompromised, the patient presents with chronic and recurrent infections, including Pneumocystis pneumonia, CMV infections, mycobacteriosis, Cryptosporidiosis, Candidiasis, Toxoplasmosis, etc. This stage is referred to as AIDS-related complex. MLS 3C YONGQUE  MLS 13A: Mycology and Virology RNA VIRUSES 2nd SEMESTER | S.Y 2023 - 2024 As immune function continues to deteriorate, the infections become more severe DIAGNOSIS and life-threatening. This stage is referred to as AIDS or full-blown AIDS. Serology HIV has also been associated with malignant conditions (Kaposi sarcoma), cancer, CPE - Infected T Cell shows “flower-shaped nucleus” which will later become and B cell lymphomas. leukemic Kaposi sarcoma - disease in which cancer cells are found in the skin or mucous membranes that line the GI tract, from mouth to anus, including the stomach and intestine. These tumors appear as purple patches or RHABDOVIRUS nodules on the skin and/or mucous membranes and can spread to lymph nodes and lungs. Diagnosis is by clinical history, serology, and detection of viral antigens or RNA. FAMILY: Rhabdoviridae Most serologic tests are screened using ELISA; all reactive samples are repeated in GENUS: Lyssavirus duplicate. Repeatedly reactive samples must be confirmed through Western blot VIRION: enveloped, rod-shaped or assay. bullet-shaped, helical capsid symmetry Once a patient is determined to be HIV (+), the stage of the disease is then GENOME: non-segmented, (-) sense, ssRNA determined. Staging is based on CD4+ cell counts and the presence of various MULTIPLICATION: R (CYTOPLASM); AM (CM) opportunistic infections. EXIT: buds from the plasma membrane Viral load can be determined by reverse transcriptase-polymerase chain reaction INFECTS: Muscle (initial replication) and (RT-PCR) neurons DISEASES MOT: infectious saliva, aerosol HIV-1 - cosmopolitan distribution; virus similar to SIV (chimpanzee) HIV-2 - common in West Africa; “slim” virus similar to SIV (sooty mangabeys) Sooty mangabeys - a primate that is used in biomedical AIDS research and is a natural host of the Simian DISEASES immunodeficiency virus (SIV), the disease from which HIV Rabies (madness, rage, fury) + Lyssa (frenzy) is derived. Cat, Dog, Raccoon animal bites Asymptomatic HIV The rabies virus gains entry into humans by animal bites as well as contact with Acute flu-like/IM-like disease bats. AIDS and AIDS associated infections Virus first infects the muscle tissue but preferentially infects neurons. (atypical Mycobacterial infection, The virus migrates along the peripheral nerves to the CNS. Pneumocystis carinii pneumonia) Disease progresses to produce convulsions, coma, and fatal encephalitis. Kaposi sarcoma Humans are dead-end host (they do not produce enough virus to shed to the environment because death follows the infection) DIAGNOSIS Serology techniques (EIA, Western Blot) PRODROMAL STAGE: Fever, headache, malaise, fatigue, paresthesia, tingling pain RT-PCR around bite site. SENSORY EXCITATION PHASE: hyperactivity, hallucinations, agitation, meningismus, RETROVIRUS (HTLV) seizures, hydrophobia, painful spasms in the pharynx, increased salivation leads to DISEASES drooling. Can cause adult T-cell leukemia/lymphoma (ATL) COMA/PARALYSIS STAGE: paralysis and respiratory dysfunction lead to death. HTLV-1: ATLL (Adult T Cell Leukemia/Lymphoma) and HTLV-1 associated myelopathy DUMB/FURIOUS RABIES: skips the excitation phase or tropical spastic paraparesis (HAM/TSP) ○ Dumb rabies: 100% fatal, coma, paralysis HTLV-2: Hairy Cell Leukemia (rarely) and spastic myelopathy ○ Furious rabies: virus reaches limbic system, delirium, coma, respiratory Tax protein - inactivates p53, a tumor suppressive protein; causes mitogenesis of arrest, death CD4+ cells MLS 3C YONGQUE  MLS 13A: Mycology and Virology RNA VIRUSES 2nd SEMESTER | S.Y 2023 - 2024 DIAGNOSIS Medical history of animal bites and a (+) direct fluorescent-antibody test FA staining of infected cell/tissues (Negri bodies), EM, PCR TREATMENT A rabies vaccine is available to prevent infection. It is only administered to those at risk for exposure to the rabies virus. Post-exposure treatment is effective if administered within 72 hours. Without rapid treatment, the infection is essentially 100% fatal. TOGAVIRUS FAMILY: Togaviridae ARBO - (Alphaviruses) - Encephalitis virus Non-ARBO - Rubella virus VIRION: enveloped, spherical, icosahedral capsid GENOME: non-segmented, (+) sense, ssRNA MULTIPLICATION: RA (CYTOPLASM); M (CM) EXIT: buds from the plasma membrane INFECTS: epithelium (nasopharynx), lymph nodes, endothelium MOT: ○ ARBOvirus - usually mosquito ○ Rubella - respiratory droplet, transplacental, feces, urine DISEASES Arthralgia (Chikungunya virus) Equine encephalitis virus (WEE,EEE) Rubella - little red, German measles Congenital rubella may lead to mental retardation and organ malformation (when contracted during the 1st trimester of pregnancy) DIAGNOSIS Serology Interference Test (using Echo virus Type A) MLS 3C YONGQUE