RNA Viruses (Paramyxoviridae & Rubella) PDF

RNA Viruses: Paramixoviridae and Rubella Virus Helen Kalandarishvili UG 2023  NEGATIVE-STRANDED - RNA VIRUSES  The virion RNA is negative sense (complementary to mRNA) and must therefore be copie...

RNA Viruses: Paramixoviridae and Rubella Virus 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 Negative-STRANDED Enveloped Orthomyxoviruses RNA VIRUSES Orthomyxoviruses Paramyxoviruses Filoviruses Rhabdoviruses Bunyaviruses Arenaviruses Filoviruses Arenaviruses Bunyaviruses Rhabdoviruses PARAMYXOVIRUSES  one piece of single-stranded not segmented RNA composed of  a helical nucleocapsid  an outer lipoprotein envelope - covered with spikes  which contain hemagglutinin, neuraminidase, or a fusion protein that causes cell fusion and, in some cases, hemolysis  The virion contains an RNA-dependent RNA polymerase  The genome is therefore not infectious.  These viruses have narrow host ranges in contrast to influenza viruses.  Most of the members are monotypic and antigenically stable. PARAMYXOVIRUSES Structure and composition  Most paramyxoviruses contain six structural proteins.  Three proteins are complexed with the viral RNA and form the nucleoprotein (N or NP)  NP forms the helical nucleocapsid (13-18 nm in diameter)  represents the major internal protein and two large proteins ( P & L), HN/H/G:  are involved in the viral polymerase activity  Hemagglutinin-neuraminidase (HN) in mumps and PIV (transcription and RNA replication).  Hemagglutinin (H) only in measles  Glycoprotein (G) in RSV ,hMPV; no hemagglutinin or neuraminidase activity PARAMYXOVIRUSES Structure and composition  Nucleocapsid is surrounded by a lipid envelope that is studded with 8- to 12-nm spikes of two different transmembrane glycoproteins.  Three proteins participate in the formation of the viral envelope.  The larger glycoprotein (HN or H or G) may possess hemagglutination and neuraminidase activities and is responsible for attachment to the host cell.  The other glycoprotein (F) mediates membrane fusion and hemolysin activities.  Matrix (M) protein underlies the viral envelope with affinity for both the nucleoprotein (NP) and the viral surface glycoproteins and is important in virion assembly.  The pneumoviruses contain two additional small envelope proteins (M2-1 and SH). PARAMYXOVIRUSES PARAMYXOVIRUSES Structure Paramyxovirus electron micrograph PARAMYXOVIRUSES Replication Virus Attachment, Penetration, and Uncoating Paramyxoviruses attach to host cells via the hemagglutinin glycoprotein (HN, H, or G protein). Virion envelope fuses with the cell membrane by the action of the fusion glycoprotein F1 cleavage product. The Viral nucleocapsid is released directly into the F1 protein undergoes complex refolding cell. during this process For the measles virus, the receptor is the membrane CD46 or the CD150 molecule. Paramyxoviruses are able to If the F0 precursor is not cleaved, it has no bypass internalization fusion activity; through endosomes. No virion penetration;virus particle can’t initiate infection. Fusion by F1 occurs at the neutral pH of the extracellular environment PARAMYXOVIRUSES Replication Transcription, Translation, and RNA Replication Paramyxoviruses contain a Messenger RNA ( mRNA) transcripts are made in the cell nonsegmented, negative-strand RNA cytoplasm by the viral RNA polymerase genome. (no dependence on cell nuclear functions). Viral proteins are synthesized in the cytoplasm The mRNAs are much smaller than  quantity of each gene product corresponds to the level of genomic size mRNA transcripts from that gene. each represents a single gene.  Viral glycoproteins are synthesized and glycosylated in the secretory pathway. The viral polymerase protein complex (P and L proteins) is responsible for viral genome replication PARAMYXOVIRUSES Replication Maturation step Progeny nucleocapsids form in the cytoplasm  Migrate to the cell surface.  attracted to sites on the plasma membrane (studded with viral HN/H/G and Paramyxoviruses mature by F0 glycoprotein spikes). budding from the cell  M protein is essential for particle formation, probably serving to link the viral surface. envelope to the nucleocapsid. During budding, most host Neuraminidase activity of the HN proteins are excluded from the protein (parainfluenza and mumps membrane. viruses) may prevent self-aggregation In presence of appropriate host cell of virus particles. proteases  Fusion proteins in the plasma membrane will be activated  fusion of adjacent cell membranes results in formation of large syncytia Syncitium  is a large cell-like structure filled with cytoplasm containing many nuclei.  Syncytium formation is a common response to paramyxovirus infection.  Acidophilic cytoplasmic inclusions are regularly formed – may reflect sites of viral synthesis. PARAMYXOVIRUSES PARAMYXOVIRUSES Formation of giant cells (syncytia) in measles pneumonia. Notice the eosinophilic inclusions in both the cytoplasm and nuclei. Classification PARAMYXOVIRUSES Paramyxovirinae Rubulavirus Mumps virus, Parainfluenza virus 2,4 Respirovirus Parainfluenza virus 1,3 Henipavirus Hendra virus, Nipah virus Morbillivirus Measles virus Pneumovirinae Pneumovirus Respiratory syncytial virus Metaneumovirus Human metapneumovirus PARAMYXOVIRUSES Respiratory syncytial virus  The most important agents of respiratory infections of infants and young and the parainfluenza children viruses  Causative agents of two of the most common contagious diseases of childhood  Paramyxoviruses are the major respiratory pathogens in the age group