Virus can fuse either directly to the plasma membrane receptor-mediated fusion or after being swallowed into an endosome. Which of these routes is followed depends on the type of virus. In fusion with the plasma membrane, the virus binds to a protein in the cell membrane. The function of this cellular protein a receptor for the virus, shown in green is perverted to induce a conformational change in the viral fusion protein, leading to fusion.
In either case, the viral genome passes through a fusion pore into cytosol, and infection is initiated. To see this figure in color, go online. Viral genetic material is relatively small, encoding only a few proteins. All enveloped viruses contain fusion proteins, which are the molecules responsible for fusing the envelope to a cellular membrane. The precise genetic material, the amino acid sequence, and details in structure of a fusion protein are unique for each type of virus.
Consequently, broad-spectrum antiviral drugs do not exist, and specific vaccines and drugs typically need to be developed for each virus type.
The viral surface of an individual virion contains multiple copies of its fusion protein. Influenza virus, for example, typically contains — copies, whereas HIV contains only about a dozen copies 1 , 2. Because enveloped viruses use similar mechanisms for delivery of genetic material into cells, there may be ways to prevent infection before viral entry that would be effective for large numbers of different viruses.
The membrane that is the skin of a cell and an enveloped virion, and is the gateway of viral entry, consists of lipids and proteins. Lipids are roughly linear molecules of fat that are attached at one end to a water-soluble headgroup. Lipids provide the cohesion that keeps biological membranes intact. They spontaneously arrange themselves into a lipid bilayer because oily fat does not mix with water.
The headgroups of one monolayer face an external aqueous solution, whereas the headgroups of the other monolayer face the interior of the cell. Integral membrane proteins, such as viral fusion proteins, are inserted into the bilayer and project out from the lipid surface into the external solution-like icebergs. Membranes are able to fuse to each other because they are fluid 3 , and the lipids provide fluidity to the membrane. Viruses initially stick to cell membranes through interactions unrelated to fusion proteins.
The virus surfs along the fluid surface of the cell and eventually the viral fusion proteins bind to receptor molecules on the cell membrane 4. If only binding occurred, the two membranes would remain distinct. Fusion does not happen spontaneously because bilayers are stable. Fusion proteins do the work of prodding lipids from their initial bilayer configuration. These proteins cause discontinuities in the bilayers that induce the lipids of one membrane e. Fusion proceeds in two major steps Fig.
In the second step, the fusion proteins disrupt this single bilayer to create a pore that provides an aqueous pathway between the virus and the cell interior. It is through this fusion pore that the viral genome gains entry into a cell and begins infection. The steps of fusion. Virus binds to specific receptors each illustrated as a small cactus on a cell membrane. Initially, four monolayers in blue separate the two interior aqueous compartments. After fusion peptides insert into the target membrane, monolayers that face each other merge and clear from the merged region.
The noncontacting monolayers bend into the cleared region and come into contact with each other, forming a new bilayer membrane known as a hemifusion diaphragm. At this point hemifusion , only two monolayers separate the compartments. The fusion protein acts as a nutcracker to force the formation of a pore within the hemifusion diaphragm. This establishes continuity between the two aqueous compartments and fusion is complete.
Hemifusion and pore formation appear to require comparable amounts of work, but the exact amount of energy needed for each step is not yet known 5.
These energetic details may be important because the more work required to achieve a step, the easier it may be to pharmacologically block that step. These energies are supplied by the viral fusion proteins, which are essentially molecular machines.
Some of their parts move long distances during the steps of fusion. Fusion proteins can be thought of as a complex assembly of wrenches, pliers, drills, and other mechanical tools. Because fusion is not spontaneous, discontinuities must be transiently created within the bilayer that allows water to reach the fatty, oily interior of the membrane.
Even a short-lived exposure of a small patch of the fatty interior to water is energetically costly. Similarly, creating a pore in a hemifusion diaphragm requires exposure of the bilayer interior to water 6.
In contrast, pore enlargement needs no such exposure. Nevertheless, pore enlargement requires the most amount of work in the fusion process. Energy is also needed because of another fundamental property of bilayer membranes. Biological membranes have shapes that are determined by their precise lipids and the proteins associated with them 7. Work is required to force membranes out of their spontaneous shape, which is the shape of lowest energy.
The fusion pore that connects the virus and cell is roughly an hourglass shape 8. The wall of a fusion pore is a membrane with components that are a mixture of the two original membranes. An hourglass shape deviates significantly from the spontaneous shape of the initial membranes that constitute the pore. The greater the diameter of the pore, the greater is the area of the lining membrane, and so pore expansion is a highly energy consuming process.
In fact, it appears that more energy is required for pore expansion than for hemifusion or pore formation. All viral fusion proteins contain a greasy segment of amino acids, referred to as a fusion peptide or fusion loop. Soon after activation of the fusion protein, the fusion peptide inserts into the target membrane either plasma or endosomal.
At this point, two extended segments of amino acids are anchored to the membranes: the fusion peptides in the target membrane and the membrane-spanning domains of the fusion proteins in the viral envelope Fig.
The fusion proteins continue to reconfigure, causing the two membrane-anchored domains to come toward each other. This pulls the viral envelope and cellular membrane closely together 9. The fusion proteins exert additional forces, but exactly what these forces are and how they promote fusion remains unknown. A virion engulfed into an endosome is like a Trojan horse, because the cell perceives the virus particle as food. Fusion of viruses within endosomes depends critically on the acidic environment.
By breaking molecular bonds, acid triggers the conformational changes in the fusion protein that lead to the sequential steps of membrane fusion. Viroids are thought to interfere with a plant's metabolism leading to underdevelopment.
They disrupt plant protein production by interrupting transcription in host cells. The transcribed DNA message is used to produce proteins.
Viroids cause a number of plant diseases that severely impact crop production. Some common plant viroids include the potato spindle tuber viroid, peach latent mosaic viroid, avocado sunblotch viroid, and the pear blister canker viroid. Satellite viruses are infectious particles that are capable of infecting bacteria, plants, fungi, and animals. They code for their own protein capsid, but they rely on a helper virus in order to replicate.
Satellite viruses cause plant diseases by interfering with specific plant gene activity. In some instances, plant disease development is dependent upon the presence of both the helper virus and its satellite. While satellite viruses alter the infectious symptoms caused by their helper virus, they do not influence or disrupt viral replication in the helper virus. Currently, there is no cure for plant viral disease.
This means that any infected plants must be destroyed for fear of spreading disease. The best methods being employed to combat plant viral diseases are aimed at prevention.
These methods include ensuring that seeds are virus-free, control of potential virus vectors through pest control products, and ensuring that planting or harvesting methods do not promote viral infection. Actively scan device characteristics for identification. Use precise geolocation data. Select personalised content. Create a personalised content profile. Measure ad performance. Select basic ads. Viruses can infect only certain species of hosts and only certain cells within that host.
Specific host cells that a virus must occupy and use to replicate are called permissive. In most cases, the molecular basis for this specificity is due to a particular surface molecule known as the viral receptor on the host cell surface.
A specific viral receptor is required for the virus to attach. In addition, differences in metabolism and host-cell immune responses based on differential gene expression are a likely factor in determining which cells a virus may target for replication. A virus must use its host-cell processes to replicate. The viral replication cycle can produce dramatic biochemical and structural changes in the host cell, which may cause cell damage.
These changes, called cytopathic effects , can change cell functions or even destroy the cell. The symptoms of viral diseases result both from such cell damage caused by the virus and from the immune response to the virus, which attempts to control and eliminate the virus from the body. Many animal viruses, such as HIV human immunodeficiency virus , leave the infected cells of the immune system by a process known as budding , where virions leave the cell individually.
During the budding process, the cell does not undergo lysis and is not immediately killed. However, the damage to the cells that the virus infects may make it impossible for the cells to function normally, even though the cells remain alive for a period of time. Most productive viral infections follow similar steps in the virus replication cycle: attachment, penetration, uncoating, replication, assembly, and release Figure 1.
A virus attaches to a specific receptor site on the host cell membrane through attachment proteins in the capsid or via glycoproteins embedded in the viral envelope.
The specificity of this interaction determines the host—and the cells within the host—that can be infected by a particular virus. This can be illustrated by thinking of several keys and several locks, where each key will fit only one specific lock. Watch this video to learn how influenza attacks the body. Viruses may enter a host cell either with or without the viral capsid. Plant and animal viruses can enter through endocytosis as you may recall, the cell membrane surrounds and engulfs the entire virus.
Some enveloped viruses enter the cell when the viral envelope fuses directly with the cell membrane. Once inside the cell, the viral capsid degrades, and then the viral nucleic acid is released and becomes available for replication and transcription. The replication mechanism depends on the viral genome. DNA viruses usually use host-cell proteins and enzymes to replicate the viral DNA and to transcribe viral mRNA, which is then used to direct viral protein synthesis. The viral mRNA directs the host cell to synthesize viral enzymes and capsid proteins, and assemble new virions.
Of course, there are exceptions to this pattern. If a host cell does not provide the enzymes necessary for viral replication, viral genes supply the information to direct synthesis of the missing proteins.
Reverse transcription never occurs in uninfected host cells—the enzyme reverse transcriptase is only derived from the expression of viral genes within the infected host cells. This approach has led to the development of a variety of drugs used to treat HIV and has been effective at reducing the number of infectious virions copies of viral RNA in the blood to non-detectable levels in many HIV-infected individuals. The last stage of viral replication is the release of the new virions produced in the host organism, where they are able to infect adjacent cells and repeat the replication cycle.
Influenza virus is packaged in a viral envelope that fuses with the plasma membrane. This way, the virus can exit the host cell without killing it. What advantage does the virus gain by keeping the host cell alive? Watch this video on viruses, identifying structures, modes of transmission, replication, and more.
This feature of a virus makes it specific to one or a few species of life on Earth. On the other hand, so many different types of viruses exist on Earth that nearly every living organism has its own set of viruses trying to infect its cells. Even prokaryotes, the smallest and simplest of cells, may be attacked by specific types of viruses.
In the following section, we will look at some of the features of viral infection of prokaryotic cells. As we have learned, viruses that infect bacteria are called bacteriophages Figure 2.
Archaea have their own similar viruses. Phage particles must bind to specific surface receptors and actively insert the genome into the host cell.
The complex tail structures seen in many bacteriophages are actively involved in getting the viral genome across the prokaryotic cell wall. When infection of a cell by a bacteriophage results in the production of new virions, the infection is said to be productive. If the virions are released by bursting the cell, the virus replicates by means of a lytic cycle Figure 3. An example of a lytic bacteriophage is T4, which infects Escherichia coli found in the human intestinal tract.
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