Viral Replication 2024 PDF

College of Medicine Viral replication Balsam Qubais Saeed, PhD October 29th 2024 Virus replication Learning objectives: Describe basic properties of viral replication Replication steps in the design of antiviral strategies Introduction Replication of viruses is very complicated process...

College of Medicine Viral replication Balsam Qubais Saeed, PhD October 29th 2024 Virus replication Learning objectives: Describe basic properties of viral replication Replication steps in the design of antiviral strategies Introduction Replication of viruses is very complicated process Virus never replicate by division They are replicate by a process in which all components of virus are assembled into intact virion Host is necessary host can be human , animal and plant Why do viruses replicate A single cell will not cause damage – must be many in numbers, Replication allows viruses to increase in numbers that may overwhelm its host A virus want to produce disease (successful parasite) Understanding replication will allows us to identify targets to prevent viral disease as well as its spread Viruses need a host to replicate Tropism – finding the right target!! Viruses do not infect all cells Must come in contact with cells & tissues in which it has evolved to infect, i.e., bacteria, plant, animals cells are recognized by specific virion-host cell interactions Invasion & replication of virus in a particular cell type is known as species-tropism Examples of Viral Target Cell Human immunodeficiency virus Helper T cell Epstein-Barr virus B cell Poliovirus Epithelial cells Rabies virus Neuron Influenza A virus Erythroid precursors  life cycle of virus The life cycle of virus. The virus life cycle could be divided into seven steps: attachment, penetration, uncoating, gene expression and replication, assembly, Maturation and release. Steps in the viral replication cycle 1. Attachment 2. Penetration (entry) 3. Uncoating 4. Genome replication 5. Assembly of virus 6. Maturation 7. Release of virus  Attachment Virus specific and inters into the host or target cell This event is electrostatic, dose not require any cellular or metabolic energy. Virus exhibits cellular tropism HIV Macrophages Rabis Muscle, neurons Hepatitis A, B, C Liver (hepatocytes) Virus has host range, and it may be narrow or broad Virus use receptors and anti receptors for attachment and entry into host cell e.g., CD4 of T-cells for HIV Cellular receptors and anti receptors are mostly protein but sometime may be glycoprotein, carbohydrates or lipids. Viral attachment to host adhesion receptor  Penetration (entry) Penetration is energy dependent process. The virus may penetrate host cell by : Endocytosis , translocation, fusion e.g., influenza membrane fusion  Penetration The virus enters the cell in a variety of ways according to the nature of the virus. Enveloped viruses Entry by fusing with the plasma membrane enveloped viruses fuse directly with the plasma membrane. Thus, the internal components of the virion are immediately delivered to the cytoplasm of the cell Entry via endosomes at the cell surface Some enveloped viruses require an acid pH for fusion to occur and are unable to fuse directly with the plasma membrane. These viruses are taken up by invagination of the membrane into endosomes. As the endosomes become acidified, the latent fusion activity of the virus proteins becomes activated by the fall in pH and the virion membrane fuses with the endosome membrane. This results in delivery of the internal components of the virus to the cytoplasm of the cell Non-enveloped viruses Non-enveloped viruses may cross the plasma membrane directly or may be taken up into endosomes. They then cross (or destroy) the endosomal membrane Uncoating Refers to removal or degradation of capsid (uncoating), there by releasing the genome into host cell. Nucleic acid has to be sufficiently uncoated that virus replication can begin at this stage. The virus genome is transported to the site where transcription \replication can begin In some there is no degradation of capsid and capsid protein play a role in viral transcription and replication Genome replication and viral protein production Viral genetic material or genome is multiplied within the host. Viral structural proteins like capsid are synthesized Type of genetic material various from virus to virus All viruses are divided into seven groups I: dsDNA viruses (e.g. Adenoviruses, ) II: ssDNA viruses (+ strand or "sense") DNA (e.g. Parvoviruses) III: dsRNA viruses (e.g. Reoviruses) IV:(+)ssRNA viruses (+ strand or sense) RNA (e.g. Coronaviruses, ) V: (−)ssRNA viruses (− strand or antisense) RNA (e.g. Rhabdoviruses) VI: ssRNA-RT viruses (+ strand or sense) RNA with DNA intermediate in life-cycle (e.g. Retroviruses) VII: dsDNA-RT viruses DNA with RNA intermediate in life-cycle (e.g. Hepadnaviruses) Assembly of virus New virus particles are assembled. During the replication of many viruses, hundreds to thousands of proteins assemble around the viral nucleic acid to form a protein shell called a capsid involves protein-protein interactions between viral structural and nonstructural proteins and the coordinated action of host factors. takes place in modified areas of the cytoplasm (pox virus Assembly ) called factories or virosomes, in adenovirus it occurs in nucleus Maturation Virus maturation is the stage of life cycle at which the virus become infectious. It involves structural, chemical, and physical changes in virus particles Release of virus Newly formed viruses are released to outside of the cell either by cell lysis of the infected cells( as in bacteriophage) or by budding as in ( paramyxovirus, retrovirus) Generally, non enveloped viruses release by cell lysis which result in the death of host cell Release of virus by budding may or may not kill the cell  Types of life cycle There are two types of life cycle commonly seen in viruses: Lytic cycle: During the lytic cycle of virulent phage, the bacteriophage takes over the cell, reproduces new phages, and destroys the cell. involves the reproduction of viruses using a host cell to manufacture more viruses; the viruses then burst out of the cell. The lytic cycle results in the destruction of the infected cell and its membrane Lysogenic cycle: In a lysogenic cycle, the phage genome also enters the cell through attachment and penetration. During the lysogenic cycle, instead of killing the host, the phage genome integrates into the bacterial chromosome and becomes part of the host. The integrated phage genome is called a prophage. a viral reproductive stage where the virus's DNA is replicated using the host cell's DNA. Most cells can go through this cycle, but it is often found in viruses that infect bacteria. When the lysogenic cell happens in a virus that infects bacteria, it is called a bacteriophage Questions