Role of host cell in viral replication

Providing habitat Provide machinery for viral replication nature of this cycle profoundly affects pathogenicity,

transmission, the responses of the immune defenses, and human measures to control viral infections

Viral life cycle consists of six stages within the host cell Attachment ycle
Penetration Uncoating Multiplication Assembly Release

Attachment
The first step in infection of a cell is attachment to the

cell surface. Attachment is via ionic interactions which are temperature-independent. The viral attachment protein recognizes specific receptors, which may be protein, carbohydrate or lipid, on the outside of the cell. Cells without the appropriate receptors are not susceptible to the virus.

Adsorption
Invasion begins when the virus encounters a susceptible

host cell and adsorbs specifically to receptor sites on the cell membrane. The membrane receptors that viruses attach to are usually glycoproteins the cell requires for its normal function. For example, the rabies virus affixes to the acetylcholine receptor of nerve cells, and the human immunodeficiency virus (HIV or AIDS virus) attaches to the CD4 protein on certain white blood cells. The mode of attachment varies between the two general types of viruses.

Adsorption in envelope viruses

In enveloped forms such as influenza virus

and HIV, glycoprotein spikes bind to the cell membrane receptors.

Adsorption in non-envelope viruses

Viruses with naked nucleocapsids

(adenovirus, for example) use molecules on their capsids that adhere to cell membrane receptors

Host Range
A virus can invade its host cell only through making an -

exact fit with a specific host molecule, the range of hosts it can infect in a natural setting is limited. This limitation, known as the host range. Specific: Hepatitis B which infects only liver cells of humans Intermediate: The poliovirus, which infects intestinal and nerve cells of primates (humans, apes, and monkeys) Broad: The rabies virus, which can infect various cells of all mammals.

Penetration/Uncoating of Animal Viruses

Animal viruses exhibit some impressive

mechanisms for entering a host cell. The flexible cell membrane of the host is penetrated by the whole virus or its nucleic acid

Penetration/Uncoating of Animal Viruses

In penetration by endocytosis , the entire virus is

engulfed by the cell and enclosed in a vacuole or vesicle. When enzymes in the vacuole dissolve the envelope and capsid, the virus is said to be uncoated, a process that releases the viral nucleic acid into the cytoplasm. The exact manner of uncoating varies, but in most cases, the virus fuses with the wall of the vesicle.

Penetration/Uncoating of Animal Viruses

Another means of viral entry into the host cell involves direct fusion of the viral envelope with the host cell membrane (as in influenza and mumps viruses)
The envelope merges directly with the cell membrane, thereby liberating the nucleocapsid into the cells interior.

Uncoating
Nucleic acid has to be sufficiently uncoated that virus

replication can begin at this stage. When the nucleic acid is uncoated, infectious virus particles cannot be recovered from the cell - this is the start of the ECLIPSE phase - which lasts until new infectious virions are made.

Synthesis: Replication and Protein Production

Free viral nucleic acid exerts control over the hosts

synthetic and metabolic machinery In general, the DNA viruses (except poxviruses) enter the host cells nucleus and are replicated and assembled there. RNA viruses are replicated and assembled in the cytoplasm, with few exceptions (such as retroviruses).

Synthesis: Replication and Protein Production

Here we provide a brief overview of the process, using

RNA viruses as a model. Almost immediately upon entry, the viral nucleic acid alters the genetic expression of the host and instructs it to synthesize the building blocks for new viruses. First, the RNA of the virus becomes a message for synthesizing viral proteins (translation). The viruses with positive-sense RNA molecules already contains the correct message for translation into proteins.

Synthesis: Replication and Protein Production

Viruses with negative-sense RNA molecules must first

be converted into a positive-sense message. Some viruses come equipped with the necessary enzymes for synthesis of viral components; others utilize those of the host. In the next phase, new RNA is synthesized using host nucleotides. Proteins for the capsid, spikes, and viral enzymes are synthesized on the hosts ribosomes using its amino acids.

Assembly of Animal Viruses: Host Cell as Factory

Toward the end of the cycle, mature virus particles are

constructed from the growing pool of parts. In most instances, the capsid is first laid down as an empty shell that will serve as a receptacle for the nucleic acid strand. Electron micrographs taken during this time show cells with masses of viruses, often in crystalline packets One important event leading to the release of enveloped viruses is the insertion of viral spikes into the hosts cell membrane so they can be picked up as the virus buds off with its envelope

Release of Mature Viruses

To complete the cycle, assembled viruses leave their

host in one of two ways: - Nonenveloped and complex viruses that reach maturation in the cell nucleus or cytoplasm are released when the cell lyses or ruptures. - Enveloped viruses are liberated by budding or exocytosis from the membranes of the cytoplasm, nucleus, endoplasmic reticulum, or vesicles.

Release of Mature Viruses

During this process, the nucleocapsid binds to the

membrane, which curves completely around it and forms a small pouch. Pinching off the pouch releases the virus with its envelope Budding of enveloped viruses causes them to be shed gradually, without the sudden destruction of the cell. Regardless of how the virus leaves, most active viral infections are ultimately lethal to the cell because of accumulated damage. Lethal damages include a permanent shutdown of metabolism and genetic expression, destruction of cell membrane and organelles, toxicity of virus components, and release of lysosomes.

Release of Mature Viruses

A fully formed, extracellular virus particle that is

virulent is called a virion. The number of virions released by infected cells is variable, controlled by factors such as the size of the virus and the health of the host cell. About 3,000 to 4,000 virions are released from a single cell infected with poxviruses, whereas a poliovirusinfected cell can release over 100,000 virions. If even a small number of these virions happens to meet another susceptible cell and infect it, the potential for rapid viral proliferation is immense.