Viral entry
Encyclopedia
Viral entry is the earliest stage of infection in the viral life cycle
, as the virus
comes into contact with the host cell
and introduces viral material into the cell. The major steps involved in viral entry are shown below. Despite the variation among viruses, the generalities are quite similar. However, the specifics are varied.
. 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 susceptible cell; a cell which holds a receptor that the virus can bind to. The receptors on the viral envelope
effectively 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 virus
or influenza
.
This basic idea extends to viruses that do not contain an envelope. Well studied examples are the viruses that infect bacteria, known as bacteriophages or simply phages. Typical phages have long tails used to attach to receptors on the bacterial surface.
bilayer, a cell's natural barrier to the outside world. The process by which this barrier is breached depends upon the virus. Types of entry are:
Through the use of green fluorescent protein
(GFP), virus entry and infection can be visualized in real-time. Once a virus enters a cell, replication is not immediate and indeed takes some time (seconds to hours).
, Herpes simplex virus
or influenza
.
of 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 vacuole
by 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
and Foot-and-mouth disease virus
.
and 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 susceptible to a virus if the virus is able to enter the cell. After the introduction of the viral particle, unpacking of the contents (viral proteins in the tegument
and the viral genome
via some form of nucleic acid
) occurs as preparation of the next stage of viral infection: viral replication
.
Viral life cycle
Viruses are similar to living organisms, however there are differences. One of the ways a virus can be seen as living is that a virus needs to replicate and create progeny. However, unlike other organisms, a virus cannot survive on its own. It is only active when replicating within a host, using a...
, as the virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
comes into contact with the host cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
and introduces viral material into the cell. The major steps involved in viral entry are shown below. 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 diffusionDiffusion
Molecular diffusion, often called simply diffusion, is the thermal motion of all particles at temperatures above absolute zero. The rate of this movement is a function of temperature, viscosity of the fluid and the size of the particles...
. 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 susceptible cell; a cell which holds a receptor that the virus can bind to. The receptors on the viral envelope
Viral envelope
Many viruses have viral envelopes covering their protein capsids. The envelopes typically are derived from portions of the host cell membranes , but include some viral glycoproteins. Functionally, viral envelopes are used to help viruses enter host cells...
effectively become connected to complementary receptors on the cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
. 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
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
, Herpes simplex virus
Herpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...
or influenza
Influenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
.
This basic idea extends to viruses that do not contain an envelope. Well studied examples are the viruses that infect bacteria, known as bacteriophages or simply phages. Typical phages have long tails used to attach to receptors on the bacterial surface.
Overview
A virus must now enter the cell, which is covered by a phospholipidPhospholipid
Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...
bilayer, a cell's natural barrier to the outside world. The process by which this barrier is breached depends upon the virus. Types of entry are:
- Attachment or Viral Adsorption: Receptors on the viral envelopeViral envelopeMany viruses have viral envelopes covering their protein capsids. The envelopes typically are derived from portions of the host cell membranes , but include some viral glycoproteins. Functionally, viral envelopes are used to help viruses enter host cells...
become connected to complementary receptors on the cell membraneCell membraneThe cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
. - 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 capsidCapsidA capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...
or genomeGenomeIn modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
is injected into the host cell's cytoplasmCytoplasmThe cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
.
Through the use of green fluorescent protein
Green fluorescent protein
The green fluorescent protein is a protein composed of 238 amino acid residues that exhibits bright green fluorescence when exposed to blue light. Although many other marine organisms have similar green fluorescent proteins, GFP traditionally refers to the protein first isolated from the...
(GFP), virus entry and infection can be visualized in real-time. Once a virus enters a cell, replication is not immediate and indeed takes some time (seconds to hours).
Entry via Membrane Fusion
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 HIVHIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
, Herpes simplex virus
Herpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...
or influenza
Influenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
.
Entry via Endocytosis
Another example is the triggered endocytosisEndocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...
of 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 vacuole
Vacuole
A vacuole is a membrane-bound organelle which is present in all plant and fungal cells and some protist, animal and bacterial cells. Vacuoles are essentially enclosed compartments which are filled with water containing inorganic and organic molecules including enzymes in solution, though in certain...
by which it was taken up, the virus must now break out of the vacuole to gain access to the cytoplasm. Examples include the poliovirus
Poliovirus
Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and member of the family of Picornaviridae.Poliovirus is composed of an RNA genome and a protein capsid. The genome is a single-stranded positive-sense RNA genome that is about 7500 nucleotides long. The viral particle is...
, Hepatitis C virus
Hepatitis C virus
Hepatitis C virus is a small , enveloped, positive-sense single-stranded RNA virus of the family Flaviviridae...
and Foot-and-mouth disease virus
Foot-and-mouth disease virus
The foot-and-mouth disease virus is the pathogen that causes foot-and-mouth disease. It is a picornavirus, the prototypical member of the Aphthovirus genus...
.
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.Aftermath
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 transcriptionTranscription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
and translation
Translation (genetics)
In molecular biology and genetics, translation is the third stage of protein biosynthesis . In translation, messenger RNA produced by transcription is decoded by the ribosome to produce a specific amino acid chain, or polypeptide, that will later fold into an active protein...
. 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 susceptible to a virus if the virus is able to enter the cell. After the introduction of the viral particle, unpacking of the contents (viral proteins in the tegument
Viral tegument
A viral tegument or tegument, more commonly known as a viral matrix, is a cluster of proteins that lines the space between the envelope and nucleocapsid of all herpesviruses. The tegument generally contains proteins that aid in viral DNA replication and evasion of the immune response, typically...
and the viral genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
via some form of nucleic acid
Nucleic acid
Nucleic acids are biological molecules essential for life, and include DNA and RNA . Together with proteins, nucleic acids make up the most important macromolecules; each is found in abundance in all living things, where they function in encoding, transmitting and expressing genetic information...
) occurs as preparation of the next stage of viral infection: viral replication
Viral replication
Viral replication is the term used by virologists to describe the formation of biological viruses during the infection process in the target host cells. Viruses must first get into the cell before viral replication can occur. From the perspective of the virus, the purpose of viral replication is...
.