MicrobiologyBytes

The interference of animal viruses with host translation was first documented in the 1960s in human fibroblasts infected with poliovirus. Further studies revealed that the halt of host translation (or “shut off”) was a general phenomenon observed in cells infected with lytic RNA and DNA viruses. Of the three steps in protein synthesis, viruses mainly affect the initiation step by hijacking or modifying the activity of key eukaryotic initiation factors (eIFs) to ensure an efficient translation of viral mRNAs and the simultaneous decline of host translation. The main targets of viruses are components of the cap-binding complex (eIF4F) that are required for the recruitment of ribosomes to mRNAs.

Infection of cultured cells with lytic animal viruses often results in “shut off”, but there is no direct or indirect evidence supporting the idea that it also should operate in whole animals infected with viruses. To address this issue, the authors of a new paper constructed a recombinant Sindbis virus (SV)-expressing reporter mRNA, the translation of which is sensitive or resistant to virus-induced shut off. As found in cultured cells, replication of SV in mouse brain was associated with a strong phosphorylation of eukaryotic initiation factor (eIF2) that prevented translation of reporter mRNA (luciferase and EGFP). Translation of these reporters was restored in vitro, in vivo, and ex vivo when a viral RNA structure, termed downstream hairpin loop, present in viral 26S mRNA, was placed at the 5′ end of reporter mRNAs.

By comparing the expression of shut off-sensitive and -resistant reporters, this work demonstrates that replication of SV in animal tissues is associated with a profound inhibition of nonviral mRNA translation. A strategy as simple as that followed here might be applicable to other viruses to evaluate their interference on host translation in infected animals.

Inhibition of host translation by virus infection in vivo. PNAS USA May 10 2010 doi: 10.1073/pnas.100411010

The eukaryotic intestinal parasite Giardia intestinalis was first described in 1681, when Antonie van Leeuwenhoek undertook a microscopic examination of his own diarrhoeal stool. Nowadays, although G. intestinalis is recognized as a major worldwide contributor to diarrhoeal disease in humans and other mammals, the disease mechanisms are still poorly understood. Owing to its reduced complexity and proposed early evolutionary divergence, G. intestinalis is used as a model eukaryotic system for studying many basic cellular processes. This review discusses recent discoveries in the molecular cell biology and pathogenesis of G. intestinalis.

Behind the smile: cell biology and disease mechanisms of Giardia species. 2010 Nature Reviews Microbiology 8, 413-422 doi:10.1038/nrmicro2317

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Strategies to reduce emissions of carbon dioxide (CO₂) from fossil fuels, and hence mitigate climate change, include energy savings, development of renewable biofuels, and carbon capture and storage (CCS). For CCS, several scenarios are being considered. One approach is capture of point-source CO₂ from power plants or other industrial sources and subsequent injection of the concentrated CO₂ underground or into the ocean. An alternative to this point-source CCS method is expansion of biological carbon sequestration of atmospheric CO₂ by measures such as reforestation, changes in land use practices, increased carbon allocation to underground biomass, production of biochar, and enhanced biomineralization. In addition to geological or oceanic CO₂ injection, novel models for point-source CCS based on accelerated weathering and biomineralization are emerging, utilizing either abiotic or biotic processes. Biomineralization of CO₂ by calcium carbonate (CaCO3) precipitation is a common phenomenon in marine, freshwater, and terrestrial ecosystems and is a fundamental process in the global carbon cycle.

Employment of cyanobacteria in biomineralization of carbon dioxide by calcium carbonate precipitation offers novel and self-sustaining strategies for point-source carbon capture and sequestration. Although details of this process remain to be elucidated, a carbon-concentrating mechanism, and chemical reactions in exopolysaccharide or proteinaceous surface layers are assumed to be of crucial importance. Cyanobacteria can utilize solar energy through photosynthesis to convert carbon dioxide to recalcitrant calcium carbonate. Calcium can be derived from sources such as gypsum or industrial brine. A better understanding of the biochemical and genetic mechanisms that carry out and regulate cynaobacterial biomineralization should put us in a position where we can further optimize these steps by exploiting the powerful techniques of genetic engineering, directed evolution, and biomimetics.

Calcifying cyanobacteria-the potential of biomineralization for carbon capture and storage. Curr Opin Biotechnol. Apr 22 2010

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In response to invasion with bacterial or viral pathogens, cells are able to mount an immediate immune response through their ability to use specialized cellular molecules, referred to as pattern recognition receptors or PRRs, to detect unusual DNA, ssRNA or dsRNA structures. This leads to induction of the interferons and pro-inflammatory cytokines that are involved in the innate immune response.

Hepatitis C virus (HCV) is one of the RNA helicase RIG-I-activating viruses, because of its 5′ppp-structured RNA, 3′-structured genomic RNA and replicative RNA duplexes. In contrast to other RIG-I activating viruses such as Sendai virus, influenza, or vesicular stomatitis virus, HCV is a poor inducer of IFN and pro-inflammatory cytokines in cell culture systems. One reason for this is that the HCV NS3/4A protease cleaves cellular proteins (MAVS), resulting in a rapid disruption of the IFN induction pathway.

A recent paper shows that HCV infection can stimulate the IFN induction pathway up to 12 hrs post-infection, whereas detection of MAVS cleavage begins at 18 hrs post-infection and is maximal at 24 hrs. The data reveal that 12 hrs post-infection, HCV promotes a rapid inhibition of IFN induction at the level of translation, indicating a new mechanism of regulation. This regulation was linked to activation of the dsRNA-activated eIF2α kinase PKR. Altogether, the results show that HCV uses PKR to control the translation of newly transcribed IFN mRNAs before sufficient NS3/4A protein can be synthesized to efficiently restrain transcription of IFN.

Although PKR is also recognized in several virus infections for its antiviral proprieties, it may be more suitable to control its action in the case of HCV infection. Therefore, a carefully-controlled use of PKR inhibitors, in conjunction with IFN/ribavirin, might be beneficial for the treatment of chronically HCV-infected patients, since it would lead to a boost in the induction of innate immunity and a sustained inhibition of the virus propagation.

Hepatitis C Virus Controls Interferon Production through PKR Activation. 2010 PLoS ONE 5(5): e10575. doi:10.1371/journal.pone.0010575

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Antibodies and other immune effectors are crucial for protecting humans from Gram-negative bacteria. Antibodies can bind outer membrane or cell surface (e.g. flagella) structures, thereby preventing adhesion, disrupting specific virulence functions, or targeting bacteria for phagocytosis. Immune effectors (antimicrobial peptides, cytokines and hormones) impinge on bacterial infections and regulate immune responses. A developing paradigm is that bacteria ‘recognize’ antibodies and immune effectors, which alert them to challenging environments, promoting resistance phenotypes and increased virulence. A broader understanding of the interactions between bacteria and antibodies and immune effectors will help define their relative contributions to pathogenesis, and perhaps indicate how we could use antibodies and immune effectors to shape bacterial phenotypes that are easier for the immune system to control.

Systems biologists use data sets from microarray (transcription networks) and yeast two-hybrid interaction (protein–protein networks) screens to define interactors in the network. A long-term goal is to understand the networks on which outer membrane structures impinge, and how to regulate them to positive effect. The challenge then becomes how to advance this perspective to develop therapeutic strategies. Currently, discovery of the protective roles of antibodies needs to be expanded from individual outer membranes of isolated bacteria. The breadth of regulation by different outer membrane-specific antibodies needs to be uncovered so bacterial phenotypes can be shaped and exploited. The current trend to antibiotic resistance indicates a need for alternative therapies that might be filled by outer membrane-specific antibodies and other immune effectors.

Antibodies and immune effectors: shaping Gram-negative bacterial phenotypes. Trends Microbiol. Mar 30 2010

The filoviruses, Marburg and Ebola, cause lethal hemorrhagic fever and are highest-priority bioterrorism agents. Filovirus particles contain a rod-like nucleocapsid and are normally filamentous, though other shapes are seen. It is poorly understood how such large filamentous particles are assembled and released from infected cells. Researchers studied Marburg virus production in infected cells using electron tomography. This technique allows virus particles to be visualized in three dimensions at different stages during assembly. They found that in early stages of virus production, highly infectious filamentous viruses are produced, whereas after prolonged infection poorly infectious spherical viruses are released. We also define the sequence of steps in filamentous virus release. The intracellular nucleocapsid first travels to the plasma membrane of the cell, where it binds laterally along its whole length. One end is then wrapped by the plasma membrane and wrapping proceeds rapidly until the virus protrudes vertically from the cell surface. The rear end of the virus particle then pinches off from the cell. They propose that other important filamentous and rod-shaped viruses also follow this series of steps of assembly and budding.

Electron Tomography Reveals the Steps in Filovirus Budding. 2010 PLoS Pathog 6(4): e1000875. doi:10.1371/journal.ppat.1000875

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Bacteria perform chemotaxis utilizing core two-component signaling systems to which have been added enhanced features of signal amplification, sensory adaptation, molecular memory and high sensitivity over a wide dynamic range. Chemoreceptors are central to the enhancements. These transmembrane homodimers associate in trimers and in clusters of signaling complexes containing from a few to thousands of receptors. Bacterial chemotaxis is mediated by two-component systems for which the capabilities of histidine kinase-response regulator signaling have been enhanced by additional components and protein modifications. With these, chemotaxis sensory systems exhibit signal amplification and sensory adaptation, detect temporal gradients through a molecular memory and respond with high sensitivity over a wide dynamic range. Chemoreceptors are central to these expanded capabilities. They carry sites of covalent modification that enable molecular memory, sensory adaptation and wide dynamic range. Receptors are homodimers that form trimers and higher order clusters of signaling complexes, structures in which interactions create signal amplification, cooperative sensing and cross-receptor adaptational assistance. This review summarizes recent progress in understanding chemoreceptors.

Bacterial chemoreceptors: providing enhanced features to two-component signaling. Curr Opin Microbiol. Jan 30 2010

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Retroviruses undergo several critical steps to complete a replication cycle. These include the complex processes of virus entry, assembly, and budding that often take place at the plasma membrane of the host cell. Both virus entry and release involve membrane fusion/fission reactions between the viral envelopes and host cell membranes. Accumulating evidence indicates important roles for lipids and lipid microdomains in virus entry and egress. This review outlines the current understanding of the role of lipids and membrane microdomains in retrovirus replication.

The Role of Lipids in Retrovirus Replication. Viruses 2010, 2(5), 1146-1180. doi:10.3390/v2051146

Today’s post is from guest blogger Melissa Tamura from Zen College Life, a directory of online degrees.

MicrobiologyBytes welcomes guest bloggers who would like to contribute occasional posts which conform to the style and content of this site. If you would like to be a guest blogger here, please email your post with a completed copyright release form to me at: alan.cann@gmail.com

There’s no doubt that antibiotics have revolutionized medicine. Before antibiotics were available, any bacterial infection was potentially lethal. However, since their widespread use started in 1945, most bacterial infections are easily treated. Despite this good news, there are some surprising side effects of common antibiotics that are not publicized.
Antibiotics are compounds that kill or inhibit the growth of bacteria. However, antibiotics are not able to differentiate between ìbadî bacteria and ìgoodî bacteria. For example, at any given time, human bodies are awash in bacteria, and many of these bacteria are actually helpful to body systems.
It’s easy to understand, for example, one of the most common side effects of antibiotics: digestive upset. Many people complain of mild nausea or diarrhea when taking a course of antibiotics. This is due to the fact that the antibiotic, while killing the harmful bacteria, has also killed some of the necessary good bacteria that exists within the digestive tract. Overall, antibiotics are considered very safe despite these sometimes annoying side effects.
Yet as more synthetic, man-made antibiotics are created and placed on the market, there appear to be some unusual side effects that no one anticipated.
One of more surprising side effects of one antibiotic is possible tendon rupture or tendonitis. This painful side effect has been linked to Levaquin, an antibiotic first produced in 1996 and later refined in 2004. According available anecdotal information, some users have torn their Achilles tendon when on this antibiotic. However, potential harm is not limited to just that tendon. It may also cause injuries to other parts of the body, such as thumbs, biceps, shoulders and hands. Research into verifying this possible side effect is ongoing.
Another unusual side effect linked to an antibiotic is mood instability. Most often associated with such antibiotics clustered in the Fluoroquinolone family, patients have reported experiencing symptoms such as nervousness, agitation, anxiety, fears centered on distrust, and suicidal thoughts. These side effects are listed for such brand antibiotics as Cipro and Floxin. Because no one is quite sure why this is the case, further study is warranted.
Augmentin, another antibiotic, has been associated with unusual bruising or bleeding. While many people can tolerate this side effect and experience no lasting harm, people with blood disorders may not fare as well. Other cited side effects of Augmentin include vaginal discharge or irritation. This side effect is probably related to the antibiotic’s destruction of some of the good bacteria that live in the uro-genital area.
Perhaps one of the more disturbing possible effects of antibiotics involves children. The U.S. National Institutes of Health describes some lasting health effects for children under age two. It appears that some children who used antibiotics very early, may exhibit such lasting symptoms as eczema, wheezing, and other asthma related problems. In scientific studies, it appears that children, who have not had to use antibiotics before age two compared to those who have, show significantly less asthma-related symptoms. Obviously, children under two are sometimes more at risk to bacterial infection, and antibiotics are absolutely necessary. Medical research is studying this phenomenon to try and limit its effect.
For anyone who has had a serious bacterial infection, the quick recovery thanks to antibiotics can’t be underestimated. However, as in anything, people need to be aware of the types of medications that they take and the possible adverse side effects. Though most side effects are short lived and not harmful, medical literature suggests that this is not always the case.