Recently, evidence has come to light indicating that some proteins with BIR motifs have functions other than blocking apoptosis, which has led to the proposal of the name BIR-containing proteins or BIRPs.
BIRPs from nematode and yeast appear to be important in regulating cytokinesis, and have no apparent anti-apoptotic function. Interestingly, survivin can regulate both apoptosis and cytokinesis. Although the function of Ac- iapl is still not clear, these results suggest that it does have a function of some kind, and that this function must be important for the virus in order for this gene to have been retained throughout evolution despite the fact that its presence retards viral replication in at least one insect species.
These proteins are involved in a variety of functions, which at first do not seem to have anything in common. One of the more interesting functions of RING motifs that has come to light recently is their involvement in the ubiquitination of proteins.
Despite significant advances in our understanding of the insect immune system and how it combats fungal and bacterial pathogens, there is little evidence to date on how insects defend themselves against viruses. The role of apoptosis in anti-viral defense in lower animals has been suspected for over a decade, 47 but the best evidence that apoptosis can be a significant anti-viral defense comes from work done with baculovirus mutants that cannot block apoptosis. Baculoviruses come in two forms, the budded virus, which consists of enveloped nucleocapsids and serves to spread infection within an infected host, and the occluded virus, which consists of enveloped nucleocapsids embedded in large protein crystals that serve to protect the virus when it is outside of the host in the environment and allow spread of infection from one host to another.
The larvae of lepidopteran insects commonly known as caterpillars can be infected either by injection of budded virus into the hemocoel blood , or by feeding occluded virus to the insects, although the normal route of infection in nature is by feeding Figure 2. Baculoviruses encode proteins, such as chitinases and proteases, that aid in the disintegration of the insect cadaver. Cell lines derived from these species differ in their response to infection with mutants of AcMNPV that lack the p35 gene.
TN cells, derived from T. When p35 mutants are used to infect larvae of these species, a correlation is observed between induction of apoptosis in the cell lines and a reduction in infectivity in the host 48 , 50 Figure 2. The basis for the lack of liquefaction is not understood.
It may be that p35 is required for successful infection of certain tissues in the insect critical for liquefaction to occur. If a large enough dose of p35 mutant virus is administered, S.
Additional evidence that apoptosis is responsible for the reduction in infectivity in S. Thus there is an excellent correlation between the ability of the virus to block apoptosis in cell culture and its ability to productively infect insect larvae. The observation in S. If the initially infected cells undergo apoptosis, this may allow the host to clear the infection, perhaps by engulfment or encapsulation of infected cells.
However, if the virus prevents apoptosis, the infection may proceed too quickly for the host defenses to be successful. The same effect may be obtained by injecting a large enough dose of p35 mutant virus. However, at this point, these are speculations, since we have no direct evidence pertaining to what is going on within the infected insect.
It has been an exciting decade since the initial discovery that baculoviruses have the ability to manipulate the apoptotic response of their insect hosts. Much progress has occurred in the determination of how the viral proteins P35 and IAP and their cellular counterparts actually function at the biochemical level in blocking apoptosis.
We have also made significant inroads into improving our understanding of how an apoptotic response can be an effective anti-viral defense. But as with all good scientific endeavors, as we continue to obtain exciting new data, more and more questions are opening up. How do baculoviruses induce apoptosis? What role, if any, do homologs of Drosophila death genes and mitochondrial factors play in baculovirus-induced cell death?
What is the biochemical mechanism of caspase inhibition by P35? Are all IAPs simply caspase inhibitors, or is the story more complicated? What is the role of ubiquitination in the function of IAP proteins? What is the importance of oligomerization of IAPs, and can the ability to form heteromeric IAP complexes regulate their activity?
Can apoptosis serve as an anti-viral defense mechanism? If so, how widespread is it? How does apoptosis influence the in vivo replication and pathogenesis of baculoviruses? What are the important tissues involved in the insect? The next decade of research on baculoviruses and apoptosis promises to answer many of these questions. Science : — CAS Google Scholar. Lu A and Miller LK. Xue D and Horvitz HR.
Nature London : — EMBO J. Apoptosis, sometimes called "cellular suicide," is a normal, programmed process of cellular self-destruction. Even though it involves cell death, apoptosis serves a healthy and protective role in our bodies.
The work of many researchers funded by the National Institutes of Health has taught us that apoptosis helps shape our physical features and organs before birth and rids our bodies of unneeded or potentially harmful cells.
Without apoptosis, we wouldn't have distinct fingers and toes or the brain cell connections to understand the words in this article. Apoptosis also helps support the immune system. For instance, it plays a critical role during viral infections, killing off invaded cells before they spill over with virus particles. This act of self-sacrifice hampers the spread of viruses and can save the whole organism.
Cells come equipped with the instructions and instruments necessary for apoptosis. Fingers develop in the paddles, but then the cells in the tissue between the fingers must die for a proper hand to form. One might say that the cells kill themselves for the greater good. They could be mutants that would become cancerous--apoptosis is therefore very important in the formation or nonformation of cancer.
Also, positive and negative selection occur among the cells of the immune system. Cells that recognize 'self' that is, ones that would attack the organism's own cells are instructed to die during this process.
Finally, cells that are infected by a virus can sometimes recognize the infection and kill themselves before the virus has time to replicate and spread to other cells. Cell death is common among plants, especially among the higher plants. The xylem in trees, through which water rises to the leaves, consists of spaces left by dead cells. Cell death occurs very visibly when deciduous trees drop their leaves in the fall. Incidentally, this is where the name 'apoptosis' comes from: it is the Greek word for the falling of leaves from trees, as well as the losing of hair from balding men--which incidentally is also thought to involve apoptosis!
Plant cells cannot move, so plants use a slash-and-burn technique to cope with infection: all the cells in an infected area may kill themselves to halt the spread of the disease. The answer gets caught up in a question of semantics between a cell choosing to die and being forced to die. But some forms of programmed death are found in unicellular organisms, including bacteria.
It is used during early development to eliminate unwanted cells; for example, those between the fingers of a developing hand. In adults, apoptosis is used to rid the body of cells that have been damaged beyond repair. Apoptosis also plays a role in preventing cancer. If apoptosis is for some reason prevented, it can lead to uncontrolled cell division and the subsequent development of a tumor.
And a leaf falls off a tree when it's dead.
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