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The article discusses two major subsets of T lymphocytes. CD8+ T cells are cytotoxic and can eliminate virus-infected host cells, whereas CD4+ T cells provide signals that help activate CD8+ T cells and antibody production by B lymphocytes. To avoid hyperactivation that may lead to irreparable tissue damage, a complex set of regulatory mechanisms CD4+ regulatory T cells exist.

The article discusses research that shows how pathogenic alphaviruses use secondary structural motifs within the 5' untranslated region (UTR) of their RNA to alter an interferon- (IFN)-stimulated gene that regulates protein synthesis, called lfit1. Topics include how interferon (IFN) signaling limits viral infection, how pathogenic viruses overcome this host response, and viruses' use of RNA structural motifs to avoid immune restriction.

The article describes the imaging of the structure of the influenza A virus genome using cryogenic electron microscopy (cryo-EM) reconstruction. Particular focus is given to the helical structure of the viral ribonucleoprotein complexes (RNPs), which contains the viral RNA bound to an RNA polymerase and multiple nucleoproteins (NPs). Other topics include the role of polymerase in viral replication, genetic transcription from viral RNPs, and RNA encapsidation by NPs. Also discussed is potential research on RNP interactions with host factors and viral proteins in virus assembly.

Influenza A virus (IAV) infection leads to variable and imperfectly understood pathogenicity. We report that segment 3 of the virus contains a second open reading frame ("X-ORF"), accessed via ribosomal frameshifting. The frameshift product, termed PA-X, comprises the endonuclease domain of the viral PA protein with a C-terminal domain encoded by the X-ORF and functions to repress cellular gene expression. PA-X also modulates IAV virulence in a mouse infection model, acting to decrease pathogenicity. Loss of PA-X expression leads to changes in the kinetics of the global host response, which notably includes increases in inflammatory, apoptotic, and T lymphocyte-signaling pathways. Thus, we have identified a previously unknown IAV protein that modulates the host response to infection, a finding with important implications for understanding IAV pathogenesis. [ABSTRACT FROM AUTHOR]

Avian A/H5N1 influenza viruses pose a pandemic threat. As few as five amino acid substitutions, or four with reassortment, might be sufficient for mammal-to-mammal transmission through respiratory droplets. From surveillance data, we found that two of these substitutions are common in A/H5N1 viruses, and thus, some viruses might require only three additional substitutions to become transmissible via respiratory droplets between mammals. We used a mathematical model of within-host virus evolution to study factors that could increase and decrease the probability of the remaining substitutions evolving after the virus has infected a mammalian host. These factors, combined with the presence of some of these substitutions in circulating strains, make a virus evolving in nature a potentially serious threat. These results highlight critical areas in which more data are needed for assessing, and potentially averting, this threat. [ABSTRACT FROM AUTHOR]

The immune system protects from infections primarily by detecting and eliminating the invading pathogens; however, the host organism can also protect itself from infectious diseases by reducing the negative impact of infections on host fitness. This ability to tolerate a pathogen's presence is a distinct host defense strategy, which has been largely overlooked in animal and human studies. Introduction of the notion of "disease tolerance" into the conceptual tool kit of immunology will expand our understanding of infectious diseases and host pathogen interactions. Analysis of disease tolerance mechanisms should provide new approaches for the treatment of infections and other diseases. [ABSTRACT FROM AUTHOR]

To establish chronic infections, viruses must develop strategies to evade the host's immune responses. Many retroviruses, including mouse mammary tumor virus (MMW), are transmitted most efficiently through mucosal surfaces rich in microbiota. We found that MMTV, when ingested by newborn mice, stimulates a state of unresponsiveness toward viral antigens. This process required the intestinal microbiota, as antibiotic-treated mice or germ-free mice did not transmit infectious virus to their offspring. MMTV-bound bacterial lipopolysaccharide triggered Toll-like receptor 4 and subsequent interleukin-6 (IL-6)-dependent induction of the inhibitory cytokine IL-10. Thus, MMTV has evolved to rely on the interaction with the microbiota to induce an immune evasion pathway. Together, these findings reveal the fundamental importance of commensal microbiota in viral infections. [ABSTRACT FROM AUTHOR]

For RNA viruses, rapid viral evolution and the biological similarity of closely related host species have been proposed as key determinants of the occurrence and long-term outcome of cross-species transmission. Using a data set of hundreds of rabies viruses sampled from 23 North American bat species, we present a general framework to quantify per capita rates of cross-species transmission and reconstruct historical patterns of viral establishment in new host species using molecular sequence data. These estimates demonstrate diminishing frequencies of both cross-species transmission and host shifts with increasing phylogenetic distance between bat species. Evolutionary constraints on viral host range indicate that host species barriers may trump the intrinsic mutability of RNA viruses in determining the fate of emerging host-virus interactions. [ABSTRACT FROM AUTHOR]

For RNA viruses, rapid viral evolution and the biological similarity of closely related host species have been proposed as key determinants of the occurrence and long-term outcome of cross-species transmission. Using a data set of hundreds of rabies viruses sampled from 23 North American bat species, we present a general framework to quantify per capita rates of cross-species transmission and reconstruct historical patterns of viral establishment in new host species using molecular sequence data. These estimates demonstrate diminishing frequencies of both cross-species transmission and host shifts with increasing phylogenetic distance between bat species. Evolutionary constraints on viral host range indicate that host species barriers may trump the intrinsic mutability of RNA viruses in determining the fate of emerging host-virus interactions. [ABSTRACT FROM AUTHOR]

T cells transformed by Herpesvirus saimiri express seven viral U-rich noncoding RNAs of unknown function called HSURs. We noted that conserved sequences in HSURs 1 and 2 constitute potential binding sites for three host-cell microRNAs (miRNAs). Coimmunoprecipitation experiments confirmed that HSURs 1 and 2 interact with the predicted miRNAs in virally transformed T cells. The abundance of one of these miRNAs, miR-27, is dramatically lowered in transformed cells, with consequent effects on the expression of miR-27 target genes. Transient knockdown and ectopic expression of HSUR1 demonstrate that it directs degradation of mature miR-27 in a sequence-specific and binding-dependent manner. This viral strategy illustrates use of a ncRNA to manipulate host-cell gene expression via the miRNA pathway. [ABSTRACT FROM AUTHOR]

Microbes rely on diverse defense mechanisms that allow them to withstand viral predation and exposure to invading nucleic acid. In many Bacteria and most Archaea, clustered regularly interspaced short palindromic repeats (CRISPR) form peculiar genetic loci, which provide acquired immunity against viruses and plasmids by targeting nucleic acid in a sequence-specific manner. These hypervariable loci take up genetic material from invasive elements and build up inheritable DNA-encoded immunity over time. Conversely, viruses have devised mutational escape strategies that allow them to circumvent the CRISPR/Cas system, albeit at a cost. CRISPR features may be exploited for typing purposes, epidemiological studies, host-virus ecological surveys, building specific immunity against undesirable genetic elements, and enhancing viral resistance in domesticated microbes. [ABSTRACT FROM AUTHOR]

Loss-of-function genetic screens in model organisms have elucidated numerous biological processes, but the diploid genome of mammalian cells has precluded large-scale gene disruption. We used insertional mutagenesis to develop a screening method to generate null alleles in a human cell line haploid for all chromosomes except chromosome 8. Using this approach, we identified host factors essential for infection with influenza and genes encoding important elements of the biosynthetic pathway of diphthamide, which are required for the cytotoxic effects of diphtheria toxin and exotoxin A. We also identified genes needed for the action of cytolethal distending toxin, including a cell-surface protein that interacts with the toxin. This approach has both conceptual and practical parallels with genetic approaches in haploid yeast. [ABSTRACT FROM AUTHOR]

HIV-1 exploits multiple host proteins during infection. We performed a large-scale small interfering RNA screen to identify host factors required by HIV-1 and identified more than 250 HIV-dependency factors (HDFs). These proteins participate in a broad array of cellular functions and implicate new pathways in the viral rife cycle. Further analysis revealed previously unknown roles for retrograde Golgi transport proteins (Rab6 and Vps53) in viral entry, a karyopherin (TNPO3) in viral integration, and the Mediator complex (Med28) in viral transcription. Transcriptional analysis revealed that HDF genes were enriched for high expression in immune cells, suggesting that viruses evolve in host cells that optimally perform the functions required for their life cycle. This effort illustrates the power with which RNA interference and forward genetics can be used to expose the dependencies of human pathogens such as HIV, and in so doing identify potential targets for therapy. [ABSTRACT FROM AUTHOR]

The interface between an infectious agent and its host represents the ultimate battleground for survival: The microbe must secure a niche for replication, whereas the host must limit the pathogen's advance. Among the host's arsenal of antimicrobial factors, the type 1 interferons (IFNs) induce potent defense mechanisms against viruses and are key in the host-virus standoff. Viruses have evolved multiple tricks to avoid the immediate antiviral effects of IFNs and, in turn, hosts have adapted use of this innate cytokine system to galvanize multiple additional layers of immune defense. The plasticity that exists in these interactions provides us with a lesson in détente. [ABSTRACT FROM AUTHOR]

Microbial life predominates in the ocean, yet little is known about its genomic variability, especially along the depth continuum. We report here genomic analyses of planktonic microbial communities in the North Pacific Subtropical Gyre, from the ocean's surface to near-sea floor depths. Sequence variation in microbial community genes reflected vertical zonation of taxonomic groups, functional gene repertoires, and metabolic potential. The distributional patterns of microbial genes suggested depth-variable community trends in carbon and energy metabolism, attachment and motility, gene mobility, and host-viral interactions. Comparative genomic analyses of stratified microbial communities have the potential to provide significant insight into higher-order community organization and dynamics. [ABSTRACT FROM AUTHOR]

Examines how small changes in viral genomes can mean a significant change in the distribution of the virus in the host. Evolution of receptor specificity by viruses; Shift in receptor usage for virus entry; Reflection of ancient evolutionary origins of viruses; Agents of horizontal gene transfers among cells.

Presents research which studied the area of major histocompatibility complex-restricted antigen presentation. Viruses in the vertebrate body; Importance of studying host-virus interactions; MHC class I-restricted antigen presentation and its evasion; Proteolysis; Peptide transport; Retention and destruction of class I molecules; Natural killer cells; Class II-restricted antigen presentation; Endocytic pathways; Negative cytokine regulation.

Focuses on viral reproduction of genomes in order to produce proteins. Importance of identification of borrowed host proteins; Essential functions performed by the proteins during viral replication; Influence of virus-host interactions in the host range and virulence of the virus; Use of the host cell by DNA viruses; Lack of preexisting cellular machinery in host cells for replication of RNA genomes; Genetic evidence suggesting that cellular proteins are also components of the replicases of plant and animal RNA viruses.

The article discusses endogenous retroviruses (ERVs). Topics include how ERVs affect the host species in which they reside, factors contributing to a reemergence of viruses that have been incorporated into vertebrate genomes after long periods of dormancy and the range of biological roles they play in their host, the genetic aspects of retroviral insertion, which adds DNA to the host genome, and an example of a useful ERV, such as that which comes with the expression of ERV envelope glycoproteins in the placenta. A diagram illustrating the functions of ERVs is presented.

Given the yearly challenge of seasonal influenza and the potential catastrophic consequences of future pandemics, the need for intensive basic and clinical influenza research is unquestionable. Although the fruits of decades of research have enabled dramatic improvements in our ability to prevent and treat influenza, many fundamental questions remain, including those related to the complex factors associated with host switching and transmission of influenza viruses. Recent public concern over two H5N1 influenza manuscripts that studied the transmissibility of influenza viruses has triggered intense discussion on dual-use research and the way forward. [ABSTRACT FROM AUTHOR]

The article explores research into the interactions between the Vpx and Vpr accessory proteins of the human immunodeficiency virus (HIV) with the host cell protein sterile alpha motif (SAM) and histidine/aspartic acid (HD) domain-containing protein 1 (SAMHD1). Vpx proteins promote viral pathogenesis and replication in HIV-1 infections and influence the proteasomal degradation of SAMHD1 in myeloid cells, while SAMHD1 blocks early replication of HIV after cell entry. The interactions between HIV proteins and SAMDH1 could present an opportunity for research in antiretroviral drug development.

The article discusses a report within the issue by Tadmor and colleagues regarding virology research. The authors note that viruses are one of the most abundant entities on Earth with the vast majority of them infecting microbes. They argue that the inability to cultivate the vast majority of them under laboratory conditions has limited scientists’ ability to study host-virus interactions. An overview of research by Tadmor and colleagues, using microfluidic digital polymerase chain reaction (PCR) to investigate the interplay between uncultured viruses and the bacteria in the hindgut of termites, is presented.

The article focuses on the study conducted by Michael Boots and Michael Mealor regarding the connection between the rise of human population to the increasing incidence of parasite transmission and virulence. The study primarily concerns on social network of host organisms as the key determinant of how parasite infectively evolves. Specifically, the study aims to prove the relationship of human population growth and mixture to the dangerous level of parasites, as well as the prediction that parasite infectivity will decrease when host movement is restricted. Details of the conducted study are posted. In addition, characteristics of these parasites and several factors that may limit the viral transmission of parasites are included.

Surveys research which studied the strategies viruses use to survive within their hosts. Bonds formed between viruses and host proteins; How viruses pirate host genes for their own genetic makeup; Presence of homologous genes in fowlpox; Viruses depending on host cell machinery for genomic replication; RNA segments of viral particles in cells' protein layers.

The article discusses virome surveys which reveal the variety and number of viruses that inhabit the human body. Topics include an overview of a virome study by researchers at Washington University (WU) School of Medicine in St. Louis, Missouri, and the role of viruses in the human body, such as preying on bacteria, which alters bacterial populations and shuffles genes from one bacteria to another.

The article presents information related to viruses. Viruses are responsible for important genetic events, from the evolution of photosynthesis to the emergence of pathogens. They play an important role in regulating the microbially dominated cycling of carbon, nitrogen and phosphorus in the world's oceans. Bacteriophages have been responsible in the development of modern molecular biological techniques. Researchers have explored how the flexibility of capsid structure can be exploited for diverse uses, including drug delivery and as precise templates for nanostructure assemblies. There are many difficulties in the biotechnological application of artificial viruses. Initial viral infection can trigger a cell into an autophagic response. It has been observed that viruses are adept at eluding host responses, but interferons can trigger a flexible network of backup responses. A new study examines a theory that viruses coexisted with the earliest organisms and perhaps helped create DNA. A research describes how gamma herpesviruses mimic and manipulate Notch and Wnt signaling.