- Viral entry
Viral entry is the earliest stage of infection in the
viral life cycle, as the viruscomes into contact with the host cell and introduces viral material into the cell. The major steps involved in viral entry are shown belowcite journal|title=Herpes simplex virus type 1 mediates fusion through a hemifusion intermediate by sequential activity of glycoproteins D, H, L, and B|author=Subramanian RP, Geraghty RJ|pmid=17299053|journal=Proceedings of the National Academy of Sciences, USA|volume=104|issue=8|date=20 Feb 2007|pages=2903–8|doi=10.1073/pnas.0608374104] . Despite the variation among viruses, the generalities are quite similar. However, the specifics are varied.
Reducing cellular proximity
A virus floating around an enclosed space with possible host cells faces a large hurdle, the thermodynamics of
diffusion. Because neutrally charged objects do not naturally clump around each other, the virus must find a way to move even near a host cell. It does this by attachment -- or adsorption --- onto a susceptiblecell; a cell which holds a receptor that the virus can bind to. The receptors on the viral envelopeeffectively become connected to complementary receptors on the cell membrane. This attachment causes the two membranes to remain in mutual proximity, favoring further interactions between surface proteins. This is also the first requisite that must be satisfied before a cell can become infected. Satisfaction of this requisite makes the cell susceptible. Viruses that exhibit this behavior include many enveloped viruses such as HIV, Herpes simplex virusor influenza.
This basic idea extends to viruses that do not contain an envelope. Well studied examples are the viruses that infect bacteria, known as
bacteriophagesor simply phages. They have long tails on which to attach to receptors the bacterial surface.
# "Attachment" or "Viral Adsorption": Receptors on the
viral envelopebecome connected to complementary receptors on the cell membrane.
# "Membrane Fusion" or "Hemifusion State": The cell membrane is punctured and made to further connect with the unfolding viral envelope.
# "Entry Pore" formation: An opening is established for the stabilization of an opening for which viral particles can then enter.
# "Viral Penetration": The viral
capsidor genomeis injected into the host cell's cytoplasm.
Entry via Membrane Fusion
A virus must now enter the cell, which is covered by a
phospholipidbilayer, a cell's natural barrier to the outside world. The process by which this barrier is breached is varied. The most well-known example is through membrane fusion. In this case, viral receptors attach to the receptors on the surface of the cell and secondary receptors may be present to initiate the puncture of the cell membrane or fusion with the host cell, followed by the unfolding of the viral envelope. In essence, the virus's envelope blends with the cell membrane, releasing its contents into the cell. Obviously, this can only be done with viruses that contain an envelope. Examples include HIV, Herpes simplex virus[Campadelli-Fiume G, Amasio M, Avitabile E, Cerretani A, Forghieri C, Gianni T, Menotti L. "The multipartite system that mediates entry of herpes simplex virus into the cell." Rev Med Virol. 2007 Sep-Oct;17(5):313-26. Review.] or influenza.
Entry via Endocytosis
Another example is the triggered
endocytosisof a cell, in which the virus tricks the cell into thinking that the virus knocking at the door is nothing more than nutrition or harmless goods. A cell naturally takes in resources from the environment and one of the ways it does so is by attaching goods onto surface receptors and engulfing them into the cell. Once inside the cell within the vacuoleby which it was taken up, the virus must now break out of the vacuole to gain access to the cytoplasm. Examples include the poliovirus, Hepatitis C virus[Helle F, Dubuisson J. "Hepatitis C virus entry into host cells." Cell Mol Life Sci. 2007 Oct 4] and Foot-and-mouth disease virus[N.J. Dimmock et al. "Introduction to Modern Virology, 6th edition." Blackwell Publishing, 2007.] .
Entry via Genetic Injection
A third and more specific example, is by simply attaching to the surface of the cell via receptors on the cell, and injecting only its gene into the cell, leaving the rest of the virus on the surface. This is restricted to viruses in which only the gene is required for infection of a cell (most positive-sense, single-stranded RNA viruses) and further restricted to viruses that actually exhibit this behavior. The best studied example includes the
phages[Sebestyén MG, Budker VG, Budker T, Subbotin VM, Zhang G, Monahan SD, Lewis DL, Wong SC, Hagstrom JE, Wolff JA. "Mechanism of plasmid delivery by hydrodynamic tail vein injection. I. Hepatocyte uptake of various molecules." J Gene Med. 2006 Jul;8(7):852-73.] .
Once a virus is in a cell, it will activate formation of proteins (either by itself or using the host) to gain full control of the host cell, if it is able to. Control mechanisms include the suppression of intrinsic cell defenses, suppression of cell signaling and suppression of host cellular
transcriptionand translation. Often, it is these cytotoxic effects that lead to the death and decline of a cell infected by a virus.
A cell is classified as
susceptibleto a virus if the virus is able to enter the cell. After the introduction of the viral particle, unpacking of the contents (viral proteinsin the tegument and the viral genomevia some form of nucleic acid) occurs as preparation of the next stage of viral infection: viral replication.
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