Virus Replication in Host Cells Flashcards
Introduction to virus replication
- The intention of every virus is to identify and invade a suitable host cell for replication or multiplication of its gene.
- After replication, the infected host cell is lysed to release copies of the virus genome which invade new hosts.
- Most viruses are host and tissue specific (tissue tropism). E.gHepatitis C only affects the liver cells
Key Viral Components
Viruses are made up of two key components:
- Genetic material: Viruses are made up either DNA or RNA, but never both.No cellular structure present (acellular)
- Capsid: Layer of protein surrounding the genetic material of a virus. Capsids are made up of smaller units called Capsomeres.
- Envelope: Extra layer of lipoprotein covering the capsid. Not present in all viruses
Role of the Capsid
Capsid protects the nucleic acid when teh virus is outside the host cell
Helps binds to a suitable host cell surface receptors using spike proteins on an envelop (if present) or transfer it’s genetic material into host cell through endocytosis if its a naked virus (that is no envelop)
e.g. Poxvirus (complex virus) lacks a typical capsid and are covered by a dense layer of lipoprotein
Roles of a genetic material
Carries gene: necessary to invade host cells.
Note the the number of genes varies for each virus (few to hundreds)
Redirect or manipulate host cell machinery into producing viral cells.
Viruses lack protein synthesizing machinery: However, they contain parts needed to evade host cells and manipulate the cell replicating machinery into producing more copies of the virus rather than normal cellular protiens.
Steps in virus genome replication
- Attachment of virionto suitable host cell.
- Entry of virus into the cell
- Transcription of virus genes into mRNA (messenger RNA) molecules.
- Translation of virus mRNA into virus proteins.
- Genome replication
- Assembly of virus proteins and genomes into new virions.
- Exit of virionsfrom host infected cells.
Note: not all viruses undergo all seven steps above, some viruses may need extra steps while some steps may occur concurrently in some viruses in which case steps 3-7 may occur at the same time
Attachment of viruses to host cells
- Viruses that infect animals and bacteria must first attach themselves to host cell surface barriers (cell wall for bacteria or cell membrane for animals)
- Cell membrane: Animal cells possess a cell membrane which the virus must attach itself to via specific cell surface receptors in order to invade the cell.
- Cell wall: Likewise, bacteria cells possess a cell wall which the virus must attach itself to via specific cell surface receptors in order to invade the cell.
- Note that virus attachment and entry in plants cell are mostly mediated by vectors.
Attachment of Animal viruses via cell receptors
- Host cell surface receptors are proteins which a virus can bind using its attachment structures prior to cell entry.
- Binding of cell surface receptors and virus attachment structures are specific like a ‘’Lock and key’’.
- Sometimes a virus may need to bind to a second host cell receptor known as a co-receptorprior to binding.
- Cell receptors and co-receptors function to mediate cell-to-cell contact and binding as well as receptors for chemokinesand growth factors.
- Binding of cell surface receptors and virus attachment structures result in a conformational change in virus proteins which initiates the binding.
- Most host cell surface receptors used by viruses contain sugar molecules (glycoproteins) composed of folded domains similar to immunoglobulin
Virus attachment sites
•Viruses possess multiple binding sites on their surfaces which is largely dependent on the absence (naked viruses) or presence of an envel
Virus attachment sites
Naked Viruses
- Nakedviruses: The attachment sites for naked viruses are on the capsid which differ in topology and may be in the form of ridges (foot and mouth disease virus), or within depressions (poliovirus). Both belong to the picornavirusgroup of viruses.
- Also, attachment sites for some naked viruses could be on specialized structures such as spikes of rotaviruses, or on fibers and knobs of adenoviruses.
- Binding of picornavirusesto host cell receptors result in major structural changes in the virion
Virus attachment sites
Enveloped viruses
•Enveloped viruses: Host cell attachment structures for enveloped viruses are on glycoproteins present on the envelope.
Virus attachment sites
Haemagglutinins
- Haemagglutinins: Some virionspossess proteins which binds to immunoglobulin causing them to clump (haemagglutination). E.g. are measles virus and influenza virus.
- Forces involved in virus-host cell binding are weak forces involving hydrogen bonding, van der Waals forces and ionic forces.
- Sugar molecules on host cell receptors and /or on the virionare involved in the binding forces
- Initial binding of viruses to host cells involves weak forces which are reversible, which become irreversible with binding of more recepto
Step 2. Entry of viruses into animal cel
- After attachment, a virus must gain entrance into host cells for replication.
- Entry: a virus must gain entry into host cells either through the cell surface or through the an endosome membrane (tiny vesicle forming part of a plasma membrane which break offs into the cytoplasm) in a process called endocytosis.
- Endocytosis: Aprocess which serve several roles for cells including nutrients uptake and defense against pathogens is hijacked by viruses to gain entry into cells
Entry of viruses into animal cells (Endocytosis
•Animal viruses gain entry into host cells through two main endocyticmechanisms:
- Clathrin-mediated endocytosis: Clathrinis a cell protein found around the inner side of cell membrane. Clathrinforms a coat around viruses resulting in pit and invagination of the cell membrane which is budded offand shed allowing the virus entry into cell. Virus examples are the adenoviruses and vesicular stomatitis virus.
- Caveolin-mediated endocytosis: Similarly viruses such as simian virus 40 coat themselves with cell membrane protein (caveolin) allowing them entry into cells through endocytosis
Naked virus entry into animal cells (Endocytosis
•Naked viruses attach and release their genome through a pore in the cell membrane by endocytosis
Enveloped virus entry into animal cells (Endocytosi
•Host cell entry may occur either by
- Endocytosis or fusion of virus envelop containing glycoprotein with plasma membrane
- Fusion of virus envelop with the cell endosome membrane.Virus fusion proteins are hiddenin the envelop and are released upon the binding of a virus to a host cell receptor resulting in a series of conformational changes.The changes fuse the virus envelop and cell membrane first from the outer layers in a process called hemifusion, followed by fusion of the inner layers, completing the fusion proces