Virus-Host Interactions PDF

Virus Host Interactions The processes where a virus infects and replicates within a host cell, manipulating it. Presented by: Aleena Sikandry Omaima Iman Narmeen Baig...

Virus Host Interactions The processes where a virus infects and replicates within a host cell, manipulating it. Presented by: Aleena Sikandry Omaima Iman Narmeen Baig Ambreen Bukhari 1 1 Introduction To Viruses 2 Different Viral Structures 3 Modes Of Entry - Endocytotic Route - Receptor Mediated Fusion Route Steps Of Fusion 4 Viruses & Proteomes (Host Proteins) 5 Comparing DNA & RNA life cycles in Host 2 01 Introduction To Viruses PART ONE Most of the phages are tadpole- Viruses as ‘obligate parasites’. shaped. Dependent on the host cell’s machinary for their replication. Phage head: hexagonal in shape, Acellular entities. composed of coat protein and Non-living. genome in the core Genome: dsDNA codes for enzymes and proteins necessary Interaction with Host Cell to replicate more viruses Tail Sheath: hollow core covered Key Point: Attachment to specific with a contractile sheath. DNA host cell receptors travels from head to bacteria 1. The virus interacts with the specific cell through sheath receptors present on the cell membrane of the host. Tail fiber: helps anchor the phage on the cell membrane 2. Attachment is the first step into entry of a virus into a host was observed in an experiment performed by d’herelle. 3 02 Different Viral Structures PART TWO Entry Modes Taken By Different Viral Structures Virus Type Shape Entry Examples Method Fusion (if Rabies (fusion), Rod-shaped enveloped) or Tobacco Mosaic Helical Viruses (Helical) Endocytosis (if Virus non-enveloped) (endocytosis) Endocytosis Polio Icosahedral Spherical (most common), (endocytosis), Viruses (Icosahedral) or Fusion (if Herpesvirus enveloped) (fusion) Direct Injection Complex (with a of genetic T4 Phage, Bacteriophages tail) material into Lambda Phage bacterial cell 4 03 Modes Of Entry PART THREE Viruses are categorized into enveloped and non- enveloped. Both of these categories share the same main steps of viral entry: interaction with the cell surface receptors of the host cell, penetration which results in release of the viral genome. After binding to receptors,which can be proteins, carbohydrates or lipids as the bacterial cell membrane consists of 50% proteins and 50% lipids by weight with the carbohydrate portions being 5- 10%, viruses use two main routes to enter the cell — The endocytic and non-endocytic routes. 5 The Endocytotic Route 1. Virus Binding: Virus binds to specific receptors via viral surface proteins. 2. Pre-Hairpin Formation: After binding, viral fusion proteins undergo a change to form a pre-hairpin structure. This structure anchors the virus to the host membrane and brings them closer together. 3. Endocytosis: Virus enters through endocytosis, forming an endosome. 4. Hairpin Formation: Inside the endosome, environmental triggers (pH change) activate fusion proteins which pull the endosomal membrane and viral membrane closer, forming a Hairpin structure. 5. Membrane Fusion: Eventually after merging, a fusion pore is created allowing release of viral genome into host cell. 6  Receptor Mediated Fusion Receptor-mediated fusion is the process by which a virus binds to specific receptors on the host cell surface, triggering fusion. Steps: 1. Viral Attachment: The virus binds to a cell receptor. 2. Fusion Protein Activation: Binding causes a conformational change in the viral fusion protein. 3. Prehairpin Formation: The fusion protein forms a prehairpin structure, which pulls the viral and host membranes together. 4. Fusion: The viral membrane fuses with the host membrane, forming a fusion pore, and releases the viral genome into the host cell. 5. Entry: The virus' genetic material enters the cell, starting the infection. 7  Steps Of Fusion The Steps of Fusion: 1. The virus attaches to specific receptors on the cell membranes. 2. Once the fusion peptides penetrate the target membrane, the layers merge. The non-contacting layers then bend into this cleared space and touch. 3. The fusion proteins result in formation of a pore within the hemifusion diaphragm. This process results in connection of the membranes, completing the fusion. The fusion process occurs in two main stages: 1. First, the monolayers of the two membranes that come into contact undergo a process called “hemifusion,” where they merge partially. This results in a hemifusion diaphragm that maintains a barrier against the viral genome's entry into the cytosol. 2. In the second stage, the fusion proteins further disrupt this single layer to form a pore, establishing an aqueous channel between the virus and the cell's interior. This fusion pore allows the viral genome to enter the cell, initiating infection. 8  Viruses & Proteomes Host Proteomes Recruited by the Virus: What Are Proteomes? 1. Hijack the cell’s machinery (e.g., to copy the viral genome, make viral proteins, and assemble new viruses). Proteomes refer to the entire set of proteins produced by a cell or organism at a given time. 2. Aid in viral gene expression: Some host proteins are used to transcribe viral genes into mRNA or assist in the The term "proteome" comes from combining “protein” and translation of mRNA into proteins. “genome”—just like the genome refers to all the genes in an organism, the proteome refers to all the proteins those genes 3. Create structures: The virus may also recruit host produce. proteins to build special structures that help in the replication process such as viral replication compartments. 9 Host Proteomes and Viral Replication Host Proteins That Help or Hinder Viral Compartments (VRCs) Replication VRCs are filled with both viral proteins and host Some host proteins are helpful to the virus, assisting in its proteins. replication and evading the immune system. The virus uses host proteins to help build these Examples: Host factors like RNA polymerase, ribosomes compartments to establish necessary machinery. might be used by the virus for transcription. The virus often restricts the host proteins that could Some host proteins act as defense mechanisms. The virus must interfere with viral replication by excluding them from either avoid or deactivate these to succeed. VRCs. Example: Apoptosis-related proteins Example: Adenovirus and Herpesvirus form VRCs. 10 05 Comparing DNA & RNA life cycles PART FIVE 11  Table Of Comparison: Feature Bacteriophage HIV Human immune cells (T-helper Host Bacteria (e.g., E. coli) cells) Virus Type DNA virus (often dsDNA) RNA retrovirus (ssRNA) Cytoplasmic (no nuclear Reverse transcription, nuclear Genome Replication involvement) integration Lysogenic cycle: integrates in Permanent integration into host Integration bacterial genome (temporary) genome Entry Mechanism Injection of DNA via tail fibers Fusion with CD4 receptors Cytoplasmic (new phages Assembly Assembly at host cell membrane assembled) Budding off from the host cell (slow Release Lysis of host cell (bacterial death) release) Host cell is destroyed in the lytic Host cell survives initially, eventually Viral Outcome cycle dies 12 Conclusion: Understanding virus-host interactions is crucial for both the prevention and treatment of viral infections. By examining the molecular mechanisms involved, including viral entry, replication, immune evasion, and pathogenesis, we can identify potential therapeutic targets. Research in this area aids in the development of vaccines, antiviral drugs, and other strategies to combat viral diseases. For example: Viral proteins: Drugs could be designed to inhibit viral enzymes like proteases or polymerases, which are crucial for the virus to replicate. Host cell receptors: Some viruses bind to specific receptors on the surface of host cells to enter them. Blocking these receptors can prevent the virus from entering and infecting cells. THANK YOU Do you have any questions?