rna_viruses_part_1 9-19-24.pdf

Microbiology and Host Defense RNA viruses: An Overview Dr. Lydia Bogomolnaya [email protected]  RNA-containing viruses Objective: - To be able to describe major groups of clinically important RNA-containing viruses RNA-containing v...

Microbiology and Host Defense RNA viruses: An Overview Dr. Lydia Bogomolnaya [email protected]  RNA-containing viruses Objective: - To be able to describe major groups of clinically important RNA-containing viruses RNA-containing viruses  RNA-containing viruses Clinically-relevant RNA viruses Virus Family Envelope Capsid Symmetry RNA Structure Clinically Important Viruses Clinical Symptoms Reovirus No Icosahedral ds linear Rotavirus Diarrhea Picornavirus No Icosahedral ss linear Poliovirus Aseptic meningitis; flaccid paralysis Echovirus Aseptic meningitis Rhinovirus Common cold Coxsackievirus Hand-foot-mouth disease, myocarditis, encephalitis Hepatitis A virus (HAV) Hepatitis A Hepevirus No Icosahedral ss linear Hepatitis E virus (HEV) Hepatitis E Caliciviruses No Icosahedral ss linear Norovirus Gastroenteritis Flaviviruses Yes Icosahedral ss linear Yellow fever Fever, nausea/vomiting, jaundice Hepatitis C virus (HCV) Hepatitis C Dengue “Breakbone fever”, joint aches West Nile virus Fever, encephalitis, flaccid paralysis Togaviruses Yes Icosahedral ss linear Rubella Lymphadenopathy, rash Retroviruses Yes Icosahedral ss linear HIV AIDS Human T-lymphotropic virus (HTLV) T-cell leukemia; HTLV-associated myelopathy Coronaviruses Yes Helical ss linear Coronavirus, SARS-CoV-2 Respiratory disease; Pneumonia Orthomyxoviruses Yes Helical ss linear Influenza virus Flu Paramyxoviruses Yes Helical ss linear Parainfluenza virus Croup Respiratory Syncytial virus (RCV) Bronchiolitis Measles Cough, cold, conjunctivitis, rash Mumps Parotitis, orchitis, pancreatitis Rhabdoviruses Yes Helical ss linear Rabies virus Fever, agitation, photophobia, hydrophobia Filoviruses Yes Helical ss linear Ebola virus Ebola hemorrhagic fever Arenaviruses Yes Helical ss circular Lymphocytic choriomeningitis virus (LCMV) Flu-like illness with headache and meningitis Lassa virus Lassa fever encephalitis Bunyaviruses Yes Helical ss circular Hantavirus Hemorrhagic fever, pneumonia, respiratory failure Delta virus Yes Uncertain ss circular Hepatitis D virus (HDV) Hepatitis D (requires HBV for infection) RNA-containing viruses Picornaviruses These are the smallest 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, Coxsackie virus, echovirus, and hepatitis A virus; (2) Rhinoviruses (more than 100 serotypes causing common colds). Rhinoviruses are acid labile and have a high density; other enteroviruses are generally acid stable and have a lower density. RNA-containing viruses Caliciviruses Caliciviruses are similar to picornaviruses but slightly larger (27–40 nm). The particles appear to have cup-shaped depressions on their surfaces. The genome is single-stranded, positive-sense RNA, 7.3–8.3 kb in size; the virion has no envelope. Important human pathogens are the noroviruses (Norwalk virus), the cause of epidemic acute gastroenteritis.  RNA-containing viruses Hepeviruses Hepeviruses are similar to caliciviruses. The particles are small (32–34 nm) and ether resistant. The genome is single-stranded, positive-sense RNA, 7.2 kb in size. It lacks a genome-linked protein (VPg). The main human pathogen is hepatitis E virus.  RNA-containing viruses Reoviruses 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. These are naked viruses (75 nm in diameter) with two icosahedral capsid coats. They have 10 or 11 segments of double-stranded linear RNA. The main human pathogen is rotavirus, which causes diarrhea, mainly in infants. The rotavirus genome has 11 segments of double-stranded RNA. RNA-containing viruses Flaviviruses Flaviviruses are enveloped viruses, 40–60 nm in diameter, with an icosahedral capsid and single-stranded, positive-sense RNA. Genome sizes vary from 9.5 to 12 kb. The name Flavi means yellow. The flaviviruses include hepatitis C virus, yellow fever virus, dengue virus, West Nile virus, Zika virus, and St. Louis and Japanese encephalitis viruses. Most members are transmitted by blood-sucking arthropods. Hepatitis C virus is a flavivirus with no known vector. RNA-containing viruses Togaviruses These are enveloped viruses with an icosahedral capsid and single-stranded, linear, non-segmented, positive-polarity RNA. The name Toga means cloak. 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.  RNA-containing viruses Coronaviruses Coronaviruses are enveloped 120- to 160-nm particles containing an unsegmented genome of positive-sense, single-stranded RNA, 27–32 kb in size. The term corona refers to the prominent halo of spikes protruding from the envelope. These viruses have narrow host ranges. Classically, human coronaviruses cause mild acute upper respiratory tract illnesses—“colds”—but more recently discovered coronaviruses cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS).  RNA-containing viruses Retroviruses These are enveloped viruses with an icosahedral capsid and two identical strands of single-stranded, linear, positive-polarity RNA. The term retro is related to the reverse transcription of the RNA genome into DNA. A virus-encoded RNA-dependent DNA polymerase (reverse transcriptase) performs this function. Only retroviruses, integrate a DNA copy of the RNA genome into cellular DNA as an obligatory step in viral replication. Retroviruses encode an integrase that performs this function. There are two medically important groups: (1) the oncovirus group, which contains human T-cell leukemia virus (HTLV); (2) the lentivirus (“slow virus”) group, which includes human immunodeficiency virus (HIV).  RNA-containing viruses Orthomyxoviruses Orthomyxoviruses are medium-sized, 80- to 120-nm enveloped viruses exhibiting helical symmetry. Particles are either round or filamentous, with surface projections that contain hemagglutinin or neuraminidase activity. The genome is linear, segmented, negative-sense, single-stranded RNA, totaling 10–13.6 kb in size. Segments range from 890 to 2350 nucleotides each. The virus matures by budding at the cell membrane. The term myxo refers to the affinity of these viruses for mucins, and ortho is added to distinguish them from the paramyxoviruses. Orthomyxoviruses include influenza viruses that infect humans or animals. The segmented nature of the viral genome permits ready genetic reassortment when two influenza viruses infect the same cell. Viral reassortment and transmission from other species is thought to explain the emergence of new human pandemic strains of influenza A viruses.  RNA-containing viruses Paramyxoviruses Paramyxoviruses are similar to but larger (150–300 nm) than orthomyxoviruses. The internal nucleocapsid measures 13–18 nm, and the linear, single- stranded, non-segmented, negative-sense RNA is 16–20 kb in size. The important human pathogens are measles, mumps, parainfluenza, metapneumovirus and respiratory syncytial viruses. These viruses have narrow host ranges. In contrast to influenza viruses, paramyxoviruses are genetically stable. RNA-containing viruses Rhabdoviruses Rhabdoviruses are enveloped virions resembling a bullet, flat at one end and round at the other, measuring about 75 × 180 nm. The term rhabdo refers to the bullet shape. The envelope has 10-nm spikes. The genome is linear, single-stranded, nonsegmented, negative-sense RNA, 11–15 kb in size. Viruses have broad host ranges. Rabies virus is the only important human pathogen.  RNA-containing viruses Filoviruses These are enveloped viruses with a helical nucleocapsid and single- stranded, linear, non-segmented, negative-polarity RNA. These viruses 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. These viruses require maximum containment conditions (Biosafety Level 4) for handling.  RNA-containing viruses Arenaviruses These are pleomorphic enveloped viruses with a helical nucleocapsid and a single-stranded, circular, negative-polarity RNA in two segments. A part of both segments is positive-polarity RNA, and the term ambisense RNA is used to describe this unusual genome. The term arena means “sand” and refers to granules on the virion surface that are nonfunctional ribosomes. Two human pathogens are lymphocytic choriomeningitis virus and Lassa fever virus. These viruses require maximum containment conditions (Biosafety level 4) in the laboratory.  RNA-containing viruses Bunyaviruses Bunyaviruses are spherical or pleomorphic, 80- to 120-nm enveloped particles. The genome is made up of a triple-segmented, single-stranded, negative-sense or ambisense RNA, 11–19 kb in overall size. Virion particles contain three circular, helically symmetric nucleocapsids about 2.5 nm in diameter and 200–3000 nm in length. The term bunya refers to the prototype, Bunyamwera virus, which is named after the place in Africa where it was isolated. The majority of these viruses are transmitted to vertebrates by arthropods (arboviruses). Hantaviruses are transmitted not by arthropods but by persistently infected rodents via aerosols of contaminated excreta. They cause hemorrhagic fevers and nephropathy as well as a severe pulmonary syndrome. RNA-containing viruses Deltavirus Hepatitis delta virus (HDV) is the only member of this genus. It is an enveloped virus with an RNA genome that is a single- stranded, negative-polarity, covalently closed circle. The symmetry of the nucleocapsid is uncertain. It is a defective virus because it cannot replicate unless HBV is present within the same cell. HBV is required because it encodes hepatitis B surface antigen (HBsAg), which serves as the outer protein coat of HDV. The RNA genome of HDV encodes only one protein, the internal core protein called delta antigen.  RNA-containing viruses Comparison of Replication Strategies of Several Important RNA Virus Families Grouping Based on Genomic RNAa Double-Stranded Positive-Strand Viruses Negative-Strand Viruses Characteristic Viruses Paramyxoviridae Picornaviridae Togaviridae Retroviridae Orthomyxoviridae Reoviridae and Rhabdoviridae Structure of genomic RNA ss ss ss ss ss ds Sense of genomic RNA Positive Positive Positive Negative Negative Segmented genome No No No Yes No Yes Two copies of non-segmented RNA Genomic RNA infectious Yes Yes No No No No Genomic RNA acts as Yes Yes Yes No No No messenger Virion-associated polymerase No No Yes Yes Yes Yes Reverse transcriptase Polyprotein precursors Yes Yes Yes No No No  RNA-containing viruses Summary of Replication Cycles of Major Virus Families Presence Intracellular Location Virus Family of Virion Replication of Formation of Multiplication Cycle (Hours)b Envelope Genome Virion Maturation Nucleocapsid RNA viruses Picornaviridae No Cytoplasm Cytoplasm Cytoplasm 6–8 Reoviridae No Cytoplasm Cytoplasm Cytoplasm 15 Togaviridae Yes Cytoplasm Cytoplasm Plasma membrane 10–24 Flaviviridae Yes Cytoplasm Cytoplasm Endoplasmic reticulum 8–10 membrane Retroviridae Yes Nucleus Cytoplasm Plasma membrane 24 Bunyaviridae Yes Cytoplasm Cytoplasm Golgi membrane 24 Orthomyxoviridae Yes Nucleus Nucleus Plasma membrane 15–30 Paramyxoviridae Yes Cytoplasm Cytoplasm Plasma membrane 10–48 Rhabdoviridae Yes Cytoplasm Cytoplasm Plasma membrane 6–10