LECTURE 15: Exit of virions from cells Waqas Nasir Chaudhry Viro100: Virology 3 Credit hours NUST Centre of Virology & Immunology Formation of virion membranes • Enveloped virions acquire their membrane envelopes by one of two mechanisms; 1. Either they modify a host cell membrane and then nucleocapsids bud through it 2. The virus directs synthesis of new membrane, which forms around the nucleocapsids Budding through cell membranes • Most enveloped viruses acquire their envelopes by budding through a membrane of the host cell • Regions of membrane through which budding will occur, become modified by the insertion of one or more species of virus protein, the vast majority of which are glycoproteins • Cell proteins may not be totally excluded from these regions and may become incorporated into virus envelopes; for example, HIV envelopes contain major histocompatibility complex class II proteins • Budding of virions involves interaction between the cytoplasmic tail of a virus glycoprotein in the membrane and another virus protein. • M (membrane, matrix) protein • M proteins have an affinity for membranes, and bind to nucleocapsids as well as to the virus glycoproteins, ‘stitching’ the two together during budding. • The vital role played by the M protein in the budding process has been demonstrated using mutants of measles virus (a paramyxovirus) and rabies virus (arhabdovirus). • Roles similar to that of the M protein are played by the M1 protein of influenza A virus and the MA (matrix) domain of the retrovirus Gag protein • Viruses that bud from the cell do so from particular regions of the plasma membrane, and if the cell is polarized then budding may take place primarily from one surface. Membrane trafficking pathways within the host cell De novo synthesis of viral membranes • A minority of viruses direct the synthesis of lipid membrane late in the replication cycle. • In some cases the membrane forms a virion envelope (e.g. poxviruses); • In other cases the membrane forms a layer below the surface of the capsid (e.g. iridoviruses) • Baculoviruses produce two types of enveloped virion during their replication. • One type of virion has the function of spreading the infection to other cells within the host, and this virion acquires its envelope by budding from the plasma membrane. • The other type of virion has the function of infecting new host individuals. • Its envelope is laid down around nucleocapsids within the nucleus and the resulting virions become incorporated into occlusion bodies Virion exit from the infected cell • The virions of many viruses are released from the infected cell when it bursts (lyses), a process that may be initiated by the virus. • Many phages produce enzymes (lysins, such as lysozymes) that break bonds in the peptidoglycan of the host bacterial cell walls. • Other phages synthesize proteins that inhibit host enzymes with roles in cell wall synthesis; this leads to weakening of the cell wall and ultimately to lysis Phage Lysins as Novel Alternatives to Antibiotics; Prof. Dr. Vincet Fischetti • Because of their modes of transmission, most plant viruses leave their host cells in ways that differ from those of animal and bacterial viruses. • Plant cells are separated from each other by thick cell walls, but in many of them there are channels, called plasmodesmata, through which the plant transports materials. • Viruses are able to spread within the host by passing from cell to cell through plasmodesmata. • For spread to new hosts many plant viruses leave the host cell as a component of the meal of a vector (e.g. an aphid or a nematode) that feeds by ingesting the contents of cells Spread of plant viruses through plasmodesmeta Reviridae Genome Replication; Conservative mode They are dsRNA viruses which replicate in the cytoplasm (indicating they have everything they need for replication and do not utilize the cells replication enzymes) and they do not fully uncoat during the process of replication. The reason for their failure to fully uncoat is that the coat is resistant to protease digestion, which prevents them from being completely destroyed by the infected cell. The mRNA used in translation is synthesized from the negative strand of the dsRNA. Each negative strand produces many positive strands. The process utilizes particle-associated transcriptase. Neither of the strands of dsRNA appear among the transcription products, and both strands remain in the uncoated core particle.