If intracellular phages are uncoated in the cytoplasm, the released nucleic acids could be sensed by the sensors cGAMP synthase DNA or RIG-I RNA , which signal through stimulator of interferon genes and mitochondrial antiviral-signaling protein, respectively.
Recently, the F. Rohwer team described how the Ig-like domain of the T4 phage Hoc capsid protein could bind mucus Barr et al. Because this protein has been detected as abundant in viromes, and highly variable, such interactions are suggested to occur frequently in the human intestine.
A better understanding of the impact of phages on immunity should help for the development of techniques such as fecal transplants, whereby a complete microbiota from an healthy individual is inoculated to a patient with severe colitis often due to Clostridium difficile infection.
Fecal transplants have been shown to represent an alternative therapy to restore eubiosis, a balanced microbial ecosystem in the human gut Allen-Vercoe et al. However, among the limits that restrain its use, is the fact that phages and viruses are also transferred during the procedure.
The impact of phages on the immune system is also actively investigated by teams working on phage therapy. Even though the phages used, and the doses applied, differ significantly from the conditions encountered in natural ecosystems, the effects observed are informative. No major adverse or stimulatory effects have been reported so far, following massive ingestion of phage preparations Gorski et al.
Phages play important and diverse roles in all bacterial ecosystems, but their precise impact on the gut microbiota is far from being understood. It is equally interesting that the gut environment differs from most other ecosystems in containing a majority of temperate phages—though virulent phages are found.
These temperate bacteriophages presumably result from spontaneous induction, and thus exist mostly as prophages integrated into the bacterial genomes. This finding influences the interpretation of results of experiments to unravel the complexities of bacteriophage-host dynamics in the gut. It might be that the action of bacteriophages on the equilibrium of the gut ecosystem is due to a large extent to their mode of existence as prophages.
The presence of an active prophage has two major implications for the bacterium. Firstly it may bring a higher sensitivity to antibiotics, some of which are known to induce lytic growth. Other stresses inducing lysogenic bacteriophages may include inflammation caused by travelers' and Crohn's disease, which have been reported to increase counts of VLP in patients' stools. But the most important contribution of bacteriophages to the gut ecosystem is probably their function as vectors of virulence and more generally of adaptation genes, whereby they contribute to a reassortment of virulence factors which results in the creation of new, virulent strains.
Though a number of high-quality investigations have recently been published, interest in the role of bacteriophages in modulating the equilibrium of the gut ecosystem is relatively recent, and the knowledge base correspondingly scant. Indeed, though the existing evidence argues for a more important role of certain of the phage-host interactions exposed in this review, there is little data on which to base a solid hypothesis.
In the future, metagenomic approaches, with their potential to determine separately the content in both bacteria and bacteriophages, will certainly provide important information on the role of bacteriophages, and notably on their potential impact on dysbiosis.
To elucidate the contribution of the various models presented in this review, a critical point will be to estimate VLP numbers in order to verify whether the global amount of phages increases or not during disease-associated shifts in species composition of the microbiota.
If this observation is indeed confirmed, biological experiments will be required in order to determine the direction or directions of causality in this association. Such models have already been used to investigate the dynamics of the phage-bacteria ecosystem killing, lysogenization, passage of the bacteriophage from one strain to another. The development of these models will allow further investigation of the phage bacteria dynamics and, importantly, the monitoring of the effect of various stresses on prophage induction and population composition possible dysbiosis.
Another, relatively simplified gut ecosystem, though not artificial, is the immature microbiota of human newborns. Following the fate of phages and bacteria in this microbiota, less diverse than that of the adult, may lead to a better understanding of the dynamics of phages and bacteria, as well as their potential perturbations during bacterial or viral infections.
More generally, virome analyses should be included in the protocols used in longitudinal studies on the microbiota of human cohorts. Apart from DNA-based analyses of the virome, phage proteins or phage-related metabolites may provide important insights. Such components produced by a stressed microbiota may be produced before any shift in the ecosystem composition, and thus constitute markers capable of anticipating dysbiosis.
Though our understanding of the involvement of bacteriophages in the equilibrium of the intestinal microbiota remains partial, the existing data on phages in human or animal-associated microbiota have established their importance, both as vectors of pathogenicity factors in the emergence of virulent strains and as dynamic players in the intestinal ecosystem.
Several pioneering investigations have recently begun to decipher the dynamics of phage-bacterium interactions and suggest avenues of research into how they may maintain homoeostasis, favor a shift to dysbiosis, or the overgrowth of opportunist pathogens. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. National Center for Biotechnology Information , U.
Front Cell Infect Microbiol. Published online Mar Colin R. Author information Article notes Copyright and License information Disclaimer. This article was submitted to the journal Frontiers in Cellular and Infection Microbiology. Received Jan 31; Accepted Mar The use, distribution or reproduction in other forums is permitted, provided the original author s or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.
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Abstract Metagenomic approaches applied to viruses have highlighted their prevalence in almost all microbial ecosystems investigated. Keywords: virome, digestive tract, community shuffling, biological weapon, horizontal transfer. Introduction Parallel to the development of metagenomics studies on microbial ecosystems Lepage et al.
Box 1 Glossary. Abundance, diversity, localization of phages in the digestive tract Lysis and lysogeny Phages essentially belong to two categories, virulent and temperate. Open in a separate window. Figure 1. Phage categories in viral fractions The viral fraction in the feces of healthy humans appears to be dominated by temperate phages, in sharp contrast with aquatic environments where virulent phages dominate Reyes et al. Phage diversity Virome studies allow for the first time to apprehend the overall phage genomic diversity, which is even greater than bacterial genomic diversity Kristensen et al.
Figure 2. Phage particle quantities As important as phage diversity, but much less reported, is the number of phage particles encountered in a given sample. Importance of the gut environment structure for phage development Theoretical studies have highlighted that phage dynamics is expected to be radically different if the environment is structured rather than homogeneous, such as in mixed aqueous solutions Heilmann et al.
Phages and dysbiosis Phage infection in the gut may be widespread, as suggested by the presence of abundant phage spacers in the CRISPR clustered regularly interspaced short palindromic repeat systems of many human gut bacteria Stern et al. Model 3: community shuffling model Figure 3C Rather than being beneficial to their bacterial host, prophages can also be detrimental as their induction results in host lysis.
Phages and emergence of new bacterial strains in the gut Model 4 The three above mentioned phage behaviors rely on the capacity of phages to lyse their host. Figure 3. Impact of phages on host immunity Mammals and their intestinal microbes live in a symbiotic relationship.
Three main interaction mechanisms between phage and the immune system have been described or suggested: Prophage-mediated changes of recognition patterns of bacteria Riley hypothesized in that phages might be involved in inflammatory bowel disease pathogenesis by changing the recognition patterns of bacteria Riley, Direct immunity modulation upon phage particles phagocytosis In addition, phages could be directly recognized by the host and trigger specific modulations.
Phages particles interacting with the mucus Recently, the F. Conclusion Phages play important and diverse roles in all bacterial ecosystems, but their precise impact on the gut microbiota is far from being understood. Conflict of interest statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. References Alexopoulos L. Networks inferred from biochemical data reveal profound differences in toll-like receptor and inflammatory signaling between normal and transformed hepatocytes.
Antibiotics in feed induce prophages in swine fecal microbiomes. MBio 2 , e—e A Canadian Working Group report on fecal microbial therapy: microbial ecosystems therapeutics. Sphingolipids from a symbiotic microbe regulate homeostasis of host intestinal natural killer T cells. Cell , — Propagation of ribonucleic acid coliphages in gnotobiotic mice. PHACCS, an online tool for estimating the structure and diversity of uncultured viral communities using metagenomic information.
BMC Bioinform. The marine viromes of four oceanic regions. PLoS Biol. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation.
Nature , — The defective prophage pool of Escherichia coli O prophage-prophage interactions potentiate horizontal transfer of virulence determinants. PLoS Pathog. Structure and distribution of an unusual chimeric genetic element encoding macrolide resistance in phylogenetically diverse clones of group A Streptococcus.
Bacteriophage adhering to mucus provide a non-host-derived immunity. The indigenous gastrointestinal microflora. Trends Microbiol. High abundance of viruses found in aquatic environments. Intracellular toll-like receptors. Immunity 32 , — Prophage contribution to bacterial population dynamics. Mobile effector proteins on phage genomes.
They do not replicate by binary fission. Instead, they divert the host cell's metabolism into synthesizing viral building blocks, which then self-assemble into new virus particles that are released into the environment. During the process of this synthesis, viruses utilize cellular metabolic energy, many cellular enzymes, and cellular organelles that they are unable to produce.
For this reason, they are incapable of sustaining an independent synthesis of their own components. The extracellular virus particle is called a virion Fig. In addition, animal viruses are not susceptible to the action of antibiotics. Virions are small, 20— nm in diameter, and pass through filters that retain most bacteria.
However, large virions for example, vaccinia, which is nm in diameter exceed the size of some smaller bacteria. The major structural components of the virion are proteins and nucleic acid, but some virions also possess a lipid-containing membranous envelope.
The shell and the nucleic acid constitute the nucleocapsid. See also: Protein. In electron micrographs of low resolution, virions appear to possess two basic shapes: spherical and cylindrical. High-resolution electron microscopy and x-ray diffraction studies of crystallized virions reveal that the "spherical" viruses are in fact polyhedral in their morphology, whereas the "cylindrical" virions display helical symmetry.
The polyhedron most commonly encountered in virion structures is the icosahedron, in which the protein molecules are arranged on the surface of 20 equilateral triangles. Based on these morphological features, viruses are classified as helical or icosahedral Fig. Certain groups of viruses do not exhibit any discernible features of symmetry and are classified as complex virions.
Further distinction is made between virions containing RNA or DNA and between those with naked or enveloped nucleocapsids. The outer protein shell of the virion furnishes protection to the most important component, that is, the viral genome, shielding it from destructive enzymes ribonucleases or deoxyribonucleases. The viral genome carries information that specifies all viral structural and functional components required for the initiation and establishment of the infectious cycle and for the generation of new virions.
This information is expressed in the alphabet of the genetic code the sequence of nucleotides and may be contained in a double-stranded or single-stranded DNA, or double-stranded or single-stranded RNA. The viral DNA may be linear or circular, and the viral RNA may be a single long chain or a number of shorter chains fragmented genomes , with each containing different genetic information.
Furthermore, some RNA viruses have the genetic information expressed as a complementary nucleotide sequence. These are classified as negative-strand RNA viruses. The discovery of this process came as a surprise to scientists because it was believed that the flow of genetic information was unidirectional from DNA to RNA to protein and could not take place in the opposite direction, that is, from RNA to DNA.
See also: Genetic code ; Reverse transcriptase ; Tumor viruses. When introduced into a susceptible cell by either chemical or mechanical means, the naked viral nucleic acid is itself infectious in most cases. In these cases, RNA has to be first transcribed and reverse-transcribed, respectively, into the proper form of genetic information before the infectious process can take place.
This task is carried out by means of an enzyme that is contained in the protein shell of the virion nucleocapsid. The whole nucleocapsid is therefore required for infectivity.
See also: Infection ; Infectious disease. Viral infection is composed of several steps: adsorption, penetration, uncoating and eclipse, and maturation and release. Adsorption takes place on specific receptors in the membrane of an animal cell. The presence or absence of these receptors determines the tissue or species susceptibility to infection by a virus. Enveloped viruses exhibit surface spikes that are involved in adsorption; however, most animal viruses do not possess obvious attachment structures.
An example is the animal herpesviruses , including herpes simplex viruses, the cause of oral and genital herpes in humans. In a process called latency , these viruses can exist in nervous tissue for long periods of time without producing new virions, only to leave latency periodically and cause lesions in the skin where the virus replicates.
Even though there are similarities between lysogeny and latency, the term lysogenic cycle is usually reserved to describe bacteriophages. Latency will be described in more detail in the next section. Figure 2. A temperate bacteriophage has both lytic and lysogenic cycles. In the lytic cycle, the phage replicates and lyses the host cell.
In the lysogenic cycle, phage DNA is incorporated into the host genome, where it is passed on to subsequent generations. Environmental stressors such as starvation or exposure to toxic chemicals may cause the prophage to excise and enter the lytic cycle. Animal viruses, unlike the viruses of plants and bacteria, do not have to penetrate a cell wall to gain access to the host cell.
The virus may even induce the host cell to cooperate in the infection process. As a protein in the viral capsid binds to its receptor on the host cell, the virus may be taken inside the cell via a vesicle during the normal cell process of receptor-mediated endocytosis.
An alternative method of cell penetration used by non-enveloped viruses is for capsid proteins to undergo shape changes after binding to the receptor, creating channels in the host cell membrane. Enveloped viruses also have two ways of entering cells after binding to their receptors: receptor-mediated endocytosis, or fusion.
Many enveloped viruses enter the cell by receptor-mediated endocytosis in a fashion similar to that seen in some non-enveloped viruses. On the other hand, fusion only occurs with enveloped virions. These viruses, which include HIV among others, use special fusion proteins in their envelopes to cause the envelope to fuse with the plasma membrane of the cell, thus releasing the genome and capsid of the virus into the cell cytoplasm.
After making their proteins and copying their genomes, animal viruses complete the assembly of new virions and exit the cell. On the other hand, non-enveloped viral progeny, such as rhinoviruses, accumulate in infected cells until there is a signal for lysis or apoptosis, and all virions are released together.
As you will learn in the next module, animal viruses are associated with a variety of human diseases. Some of them follow the classic pattern of acute disease , where symptoms get increasingly worse for a short period followed by the elimination of the virus from the body by the immune system and eventual recovery from the infection.
Examples of acute viral diseases are the common cold and influenza. Other viruses cause long-term chronic infections , such as the virus causing hepatitis C, whereas others, like herpes simplex virus, only cause intermittent symptoms. Still other viruses, such as human herpesviruses 6 and 7, which in some cases can cause the minor childhood disease roseola, often successfully cause productive infections without causing any symptoms at all in the host, and thus we say these patients have an asymptomatic infection.
Unlike the growth curve for a bacterial population, the growth curve for a virus population over its life cycle does not follow a sigmoidal curve. During the initial stage, an inoculum of virus causes infection. In the eclipse phase , viruses bind and penetrate the cells with no virions detected in the medium. The chief difference that next appears in the viral growth curve compared to a bacterial growth curve occurs when virions are released from the lysed host cell at the same time.
Such an occurrence is called a burst , and the number of virions per bacterium released is described as the burst size. In a one-step multiplication curve for bacteriophage , the host cells lyse, releasing many viral particles to the medium, which leads to a very steep rise in viral titer the number of virions per unit volume. If no viable host cells remain, the viral particles begin to degrade during the decline of the culture see Figure 8.
Figure 8. The one-step multiplication curve for a bacteriophage population follows three steps: 1 inoculation, during which the virions attach to host cells; 2 eclipse, during which entry of the viral genome occurs; and 3 burst, when sufficient numbers of new virions are produced and emerge from the host cell.
The burst size is the maximum number of virions produced per bacterium. Ebola is incurable and deadly. The outbreak in West Africa in was unprecedented, dwarfing other human Ebola epidemics in the level of mortality. Of 24, suspected or confirmed cases reported, 10, people died.
No approved treatments or vaccines for Ebola are available. While some drugs have shown potential in laboratory studies and animal models, they have not been tested in humans for safety and effectiveness. Not only are these drugs untested or unregistered but they are also in short supply. Given the great suffering and high mortality rates, it is fair to ask whether unregistered and untested medications are better than none at all.
Should such drugs be dispensed and, if so, who should receive them, in light of their extremely limited supplies? Is it ethical to treat untested drugs on patients with Ebola? On the other hand, is it ethical to withhold potentially life-saving drugs from dying patients? Or should the drugs perhaps be reserved for health-care providers working to contain the disease?
In August , two infected US aid workers and a Spanish priest were treated with ZMapp , an unregistered drug that had been tested in monkeys but not in humans. The two American aid workers recovered, but the priest died. Later that month, the WHO released a report on the ethics of treating patients with the drug. Since Ebola is often fatal, the panel reasoned that it is ethical to give the unregistered drugs and unethical to withhold them for safety concerns.
On September 24, , Thomas Eric Duncan arrived at the Texas Health Presbyterian Hospital in Dallas complaining of a fever, headache, vomiting, and diarrhea—symptoms commonly observed in patients with the cold or the flu. After examination, an emergency department doctor diagnosed him with sinusitis, prescribed some antibiotics, and sent him home. Two days later, Duncan returned to the hospital by ambulance. His condition had deteriorated and additional blood tests confirmed that he has been infected with the Ebola virus.
Further investigations revealed that Duncan had just returned from Liberia, one of the countries in the midst of a severe Ebola epidemic. On September 15, nine days before he showed up at the hospital in Dallas, Duncan had helped transport an Ebola-stricken neighbor to a hospital in Liberia.
The hospital continued to treat Duncan, but he died several days after being admitted. Figure 9. Researchers working with Ebola virus use layers of defenses against accidental infection, including protective clothing, breathing systems, and negative air-pressure cabinets for bench work. The timeline of the Duncan case is indicative of the life cycle of the Ebola virus.
The incubation time for Ebola ranges from 2 days to 21 days. This corresponds, in part, to the eclipse period in the growth of the virus population. During the eclipse phase, Duncan would have been unable to transmit the disease to others. However, once an infected individual begins exhibiting symptoms, the disease becomes very contagious. Ebola virus is transmitted through direct contact with droplets of bodily fluids such as saliva, blood, and vomit.
Duncan could conceivably have transmitted the disease to others at any time after he began having symptoms, presumably some time before his arrival at the hospital in Dallas. Once a hospital realizes a patient like Duncan is infected with Ebola virus, the patient is immediately quarantined, and public health officials initiate a back trace to identify everyone with whom a patient like Duncan might have interacted during the period in which he was showing symptoms.
Public health officials were able to track down 10 high-risk individuals family members of Duncan and 50 low-risk individuals to monitor them for signs of infection.
None contracted the disease. What is the name for the transfer of genetic information from one bacterium to another bacterium by a phage? Skip to main content. Acellular Pathogens. Search for:. The Viral Life Cycle Learning Objectives Describe the lytic and lysogenic life cycles Describe the replication process of animal viruses Describe unique characteristics of retroviruses and latent viruses Discuss human viruses and their virus-host cell interactions Explain the process of transduction Describe the replication process of plant viruses.
Think about It Is a latent phage undetectable in a bacterium? Think about It Which phage life cycle is associated with which forms of transduction?
Think about It In what two ways can a virus manage to maintain a persistent infection? Think about It What is the structure and genome of a typical plant virus? Think about It What aspect of the life cycle of a virus leads to the sudden increase in the growth curve? Unregistered Treatments Ebola is incurable and deadly. Ebola in the US On September 24, , Thomas Eric Duncan arrived at the Texas Health Presbyterian Hospital in Dallas complaining of a fever, headache, vomiting, and diarrhea—symptoms commonly observed in patients with the cold or the flu.
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