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Biological roles of HIV Nef proteins. A minireview.

The nef gene, its protein products and diverse mechanisms by which HIV pathogenicity is nef-mediated in vivo and in vitro explain the huge amount of works on this topic. Until now the following functional roles have been assigned for nef: 1. downregulation of virus replication; 2. GTP binding and GTPase activities; 3. modulation of cytoplasmic signalling; and 4. cellular (CD4 and IL-2) gene regulation. Many reports which demonstrate the possible functions of nef in viral replication and in development of AIDS have been refuted by other scientists who failed to confirm some biological activities. Host immune response against nef proteins has been claimed as an early diagnosis marker or to be involved in disease progression. Also, nef proteins have been involved in blocking of HLA antigens, in superantigen production or in crossreactivity with some cellular antigens. The role of nef is a complex one, important in establishing and maintaining viral latency in vivo and regulating virus replication in vitro.

Down-Regulation↗

[A comparative analysis of molecular-genetic peculiarities of the genomes of cholera, plague and anthrax agents and their evolutional transformations].

Cholera, plague, and anthrax, the diseases that have accounted for millions of human victims, still endanger the entire mankind by possible development of epidemic outbreaks due to their spread or application as bioterrorist agents. Generalized results of research into the genomic features of the Vibrio cholerae, Yersinia pestis, and Bacillus anthracis are discussed. Despite different frequencies of evolutional transformations occurring in their genomes, that are likely to be associated with diverse life cycles of the pathogens, clones with altered diagnostic, and virulence characteristics were shown to have a fair probability of formation. Also presented in the review, are literature data concerning the main evolutional stages for any of these pathogens, determination of new genetic variants, consideration of the mechanisms facilitating maintenance of the microbial agents during the interepidemic periods.

Anthrax↗

Toxic shock due to Streptococcus pyogenes in a rhesus monkey (Macaca mulatta).

Recent years have seen a worldwide resurgence in serious infections caused by group A streptococci. This group includes Streptococcus pyogenes, one of the most common pathogens among children which causes diverse suppurative infections, such as pharyngitis, as well as nonsuppurative infections with sequelae, such as rheumatoid fever and rheumatic heart disease. S. pyogenes produces several superantigen-like erythrogenic toxins, which are believed to be associated with pyrogenicity, erythromatous skin reactions, and various immunologic and cytotoxic effects. These toxins also can cause myocardial necrosis. In addition, recently reported streptococcal infections in obstetric human patients appear to be clinically different from classic puerperal sepsis. Here, we report a case of spontaneous streptococcal infection in a pregnant female rhesus monkey (Macaca mulatta). In addition to lesions consistent with bacteremia and toxic shock, this animal had severe cardiac lesions resembling those described in humans with rheumatic heart disease. S. pyogenes was isolated from intracardiac blood, liver, placenta, and fetal tissues. This isolate also had a unique M protein gene.

Animals↗

Generation of the (auto)-antibody repertoire: a case of narcissism?

The immune system has the tremendous task of recognizing and eliminating a practically unlimited number of foreign and often harmful substances. To reach that goal, it has evolved as an apparatus generating a vast array of different antigen receptors expressed by T and B lymphocytes. Through these receptors, the cells can recognize, and respond to, foreign structures; nevertheless, the lymphocytes do not normally react to the body's own constituents. The processes that safeguard a sufficiently broad diversity and yet prevent potentially pathogenic autoimmune reactivity are only now beginning to be elucidated. We describe some of the mechanisms that are believed to play a major role in the generation of the B lymphocyte and antibody repertoire, the induction of tolerance against autologous components and the production of pathogenic autoantibodies, once tolerance is broken.

Animals↗

Enteropathy in HIV infection.

Enteropathy occurs frequently in persons infected with human immunodeficiency virus (HIV), and symptoms related to the gut are a major cause of debility. The pathogens associated with disease are diverse, often difficult to detect, and frequently poorly responsive to any therapeutic intervention. This brief review examines HIV-related enteropathy from the perspective of symptomatology, and discusses some of the recent advances in diagnosis of specific gut disorders.

Gastrointestinal Diseases↗

Natural history and pathogenesis as they affect clinical trials.

Careful observations on the natural history of infectious diseases have been the inspiration behind many successful vaccines, including Jenner's successful demonstration of protection against smallpox. Many "experiments of nature" provide powerful data on the key components of protective immunity. An understanding of the basis of protective immunity in absolute terms or, more realistically, through the proxy of surrogates of immunity, lies at the heart of clinical trials of vaccines. An understanding of infectious disease pathogenesis is also critical in defining and distinguishing immunisation strategies that aim to prevent infection (e.g. measles vaccine) as distinct from prevention of disease (e.g. tetanus toxoid). Coupled to classical epidemiology and the careful analysis of clinical data, the tools of molecular and cell biology have revolutionised the tools available for vaccine research, including clinical trials. Molecular techniques have provided tools for investigating the population structure of pathogens. The importance of population diversity and its associated antigenic variation is a key factor in designing and carrying out clinical trials of vaccines.

Animals↗

Complex genetic networks underlying the defensive system of rice (Oryza sativa L.) to Xanthomonas oryzae pv. oryzae.

Complete resistance (CR) and partial resistance (PR) of rice (Oryza sativa L.) to its bacterial pathogen, Xanthomonas oryzae pv. oryzae (Xoo), was genetically dissected by using 2 mapping populations and 10 Xoo races. Two CR genes, 50 quantitative resistance loci, and 60 digenic interactions were identified, which showed various degrees of race specificity to the Xoo races. The complex epistasis between these loci led us to the discovery of complex genetic networks underlying the rice defensive system to Xoo. The networks consisted of two major components: one representing interactions between alleles at the R loci of rice and alleles at the corresponding avirulence loci of Xoo for CR and the other comprising interactions between quantitative resistance loci in rice and their corresponding aggressiveness loci in Xoo for PR. The race specificity of PR and its strong genetic overlap with CR indicate that PR is essentially "weaker" CR. The genetic networks discovered are expected to maintain a high level of the allelic diversity at avirulent loci in the pathogen by stabilizing selection, which may maintain a high allelic diversity at R loci in the host by the frequency-dependent selection.

Alleles↗

The emerging diversity of Rickettsia.

The best-known members of the bacterial genus Rickettsia are associates of blood-feeding arthropods that are pathogenic when transmitted to vertebrates. These species include the agents of acute human disease such as typhus and Rocky Mountain spotted fever. However, many other Rickettsia have been uncovered in recent surveys of bacteria associated with arthropods and other invertebrates; the hosts of these bacteria have no relationship with vertebrates. It is therefore perhaps more appropriate to consider Rickettsia as symbionts that are transmitted vertically in invertebrates, and secondarily as pathogens of vertebrates. In this review, we highlight the emerging diversity of Rickettsia species that are not associated with vertebrate pathogenicity. Phylogenetic analysis suggests multiple transitions between symbionts that are transmitted strictly vertically and those that exhibit mixed (horizontal and vertical) transmission. Rickettsia may thus be an excellent model system in which to study the evolution of transmission pathways. We also focus on the emergence of Rickettsia as a diverse reproductive manipulator of arthropods, similar to the closely related Wolbachia, including strains associated with male-killing, parthenogenesis, and effects on fertility. We emphasize some outstanding questions and potential research directions, and suggest ways in which the study of non-pathogenic Rickettsia can advance our understanding of their disease-causing relatives.

Animals↗

Pilot metaproteomic profiling reveals bacterial diversity and potential medical and veterinary relevance of tick microbiomes in northern Algeria.

Ticks are major ectoparasites and vectors of pathogens affecting humans, livestock, and wildlife. They harbor diverse microbial communities that may influence tick biology and interactions with microorganisms; however, functional information on tick-associated microbiomes remains limited, particularly in North Africa. In this pilot study, we applied a metaproteomic approach based on high-resolution tandem mass spectrometry to characterize bacterial communities associated with three tick species collected in Algeria: Rhipicephalus sanguineus sensu lato, Hyalomma aegyptium, and Hyalomma dromedarii. Peptide spectra were assigned to taxa using a two-step database search strategy based on NCBInr, and bacterial composition and relative abundance were compared across tick species and sampling locations. A total of 40 bacterial genera belonging to 32 families and four phyla were identified. Microbiome composition differed significantly between tick genera and collection locations, suggesting an influence of species-specific and geographical factors on microbial community structure. Dominant genera included Streptomyces, Bacillus, Clostridium, Escherichia, Flavobacterium, Paenibacillus, and Providencia. Peptides related to Coxiella spp. were frequently detected, consistent with previous reports of Coxiella-like endosymbionts in ticks. This pilot study provides a first metaproteomic characterization of tick-associated communities in Algeria. The results reveal species- and location-associated differences in microbial composition and highlight the potential of metaproteomics for exploring tick-associated microbiomes in North Africa.

Animals↗

Extensive hidden prophage diversity in Enterobacter species reveals host specificity and local distribution.

Bacteriophages are key drivers of bacterial evolution, particularly through their integration as prophages within host genomes. However, the diversity and host specificity of prophages in relevant pathogens such as Enterobacter species remain poorly characterized. In this study, we revealed the diversity of prophages, mapped their distribution and explored their relationships with their bacterial hosts. We analysed 3,661 prophage sequences identified from the genomes of 20 different Enterobacter species. This analysis uncovered an extensive hidden diversity, comprising 1,617 phage genera and 2,423 phage species - nearly 80% of which were singletons - highlighting an exceptionally rich prophage landscape. We found substantial variation in prophage species richness across host species and isolation sources, with Enterobacter kobei and environmental isolates exhibiting the highest richness. Prophage populations showed strong host specificity and limited cross-species transmission. Moreover, prophages exhibited geographic structuring and significant congruence between host and prophage phylogenies, as well as with the ecological lifestyles of their bacterial hosts. Although we found phages of the same species infecting different host species, these events were infrequent. Finally, bacterial genomes encoded diverse defence systems, mainly PDC-S07, RM type I-II and gabija, whereas only 8.9% of prophages encoded anti-defence systems, mostly anti-CBASS and anti-RM. Overall, this study provides new insights into the diversity of Enterobacter prophages and underscores their ecological and clinical relevance in shaping host adaptation and phage-host dynamics.

Prophages↗

Genetic diversity of Fusarium oxysporum strains from common bean fields in Spain.

Fusarium wilt is an endemic disease in El Barco de Avila (Castilla y León, west-central Spain), where high-quality common bean cultivars have been cultured for the last century. We used intergenic spacer (IGS) region polymorphism of ribosomal DNA, electrophoretic karyotype patterns, and vegetative compatibility and pathogenicity analyses to assess the genetic diversity within Fusarium oxysporum isolates recovered from common bean plants growing in fields around El Barco de Avila. Ninety-six vegetative compatibility groups (VCGs) were found among 128 isolates analyzed; most of these VCGs contained only a single isolate. The strains belonging to pathogenic VCGs and the most abundant nonpathogenic VCGs were further examined for polymorphisms in the IGS region and electrophoretic karyotype patterns. Isolates belonging to the same VCG exhibited the same IGS haplotype and very similar electrophoretic karyotype patterns. These findings are consistent with the hypothesis that VCGs represent clonal lineages that rarely, if ever, reproduce sexually. The F. oxysporum f. sp. phaseoli strains recovered had the same IGS haplotype and similar electrophoretic karyotype patterns, different from those found for F. oxysporum f. sp. phaseoli from the Americas, and were assigned to three new VCGs (VCGs 0166, 0167, and 0168). Based on our results, we do not consider the strains belonging to F. oxysporum f. sp. phaseoli to be a monophyletic group within F. oxysporum, as there is no correlation between pathogenicity and VCG, IGS restriction fragment length polymorphism, or electrophoretic karyotype.

Base Sequence↗

Fresh insights into processes of nonhost resistance.

Nonhost resistance confers robust protection against pathogenic invaders, and has many similarities to host resistance. Through the different steps of pathogen development, plants make use of diverse defence strategies to present obstacles to the invader. These include preformed barriers, innate immunity in response to general elicitors and, as a last option, resistance mediated by independent and simultaneously acting pairs of pathogen avr and plant R genes. Our understanding of the roles played by these obstacles is relatively poor in nonhost resistance compared to host resistance. There is an obvious need to investigate how these roles may depend on the evolutionary distance between the pathogen host and a certain nonhost plant.

Plants↗

CD8 T cell clonal expansions & aging: a heterogeneous phenomenon with a common outcome.

A highly diverse CD8 T cell repertoire is thought to be critical for maintaining appropriate immune defenses against a variety of pathogens. However, in many aged individuals, the diversity of T cell receptors is significantly reduced by the presence of large, monoclonal expansions of CD8 memory T cells. While ongoing research is focused on understanding the molecular alterations in these expansions, one major hurdle to this goal is the apparent heterogeneity of CD8 clonal expansions, which is apparent even in reductionist systems. In this review, we discuss current evidence that CD8 clonal expansions are a heterogeneous phenomenon, and our evolving understanding of what this heterogeneity tells us about CD8 memory T cell homeostasis and how it is altered in aged individuals.

CD8-Positive T-Lymphocytes↗

Post-genomic virology: the impact of bioinformatics, microarrays and proteomics on investigating host and pathogen interactions.

Post-genomic research encompasses many diverse aspects of modern science. These include the two broad subject areas of computational biology (bioinformatics) and functional genomics. Laboratory based functional genomics aims to measure and assess either the messenger RNA (mRNA) levels (transcriptome studies) or the protein content (proteome studies) of cells and tissues. All of these methods have been applied recently to the study of host and pathogen interactions for both bacteria and viruses. A basic overview of the technology is given in this review together with approaches to data analysis. The wealth of information produced from even these preliminary studies has shown the generalities, subtleties and specificities of host-pathogen interactions. Such research should ultimately result in new methods for diagnosing and treating infectious diseases.

Amino Acid Sequence↗

Sex, parasites and resistance--an evolutionary approach.

Immune systems are among the most diverse biological systems. An evolutionary arms race between hosts and rapidly evolving pathogens is supposed to be a reason for this diversity, and might explain why most eukaryotic hosts and parasites reproduce sexually. In this review, I will focus on possible benefits of sexual reproduction in hosts and parasites, using a model system consisting of a tapeworm and its two intermediate hosts, copepods and sticklebacks. We found that the hermaphroditic tapeworms can increase their infection success by reproducing sexually with a partner (outcrossing), instead of reproducing alone. The defence system of the copepods provides highly specific discrimination of antigenic characteristics of the tapeworms. This supports the finding that tapeworms benefit from outcrossing, but contradicts the conventional notion that the immune system of invertebrates, in contrast to vertebrates, is not able to react with specificity. Finally, sticklebacks seem to benefit from optimal diversity in their specific immune system. Previous studies showed that female sticklebacks prefer mates, which sire offspring with an optimal diversity in the MHC (genes involved in antigen presentation). We now found that these individuals suffer less from tapeworm infection. Furthermore, they are able to reduce the expression of an unspecific immune trait, thereby possibly avoiding harmful side effects of a highly activated, unspecific immune system.

Journal Article↗

Analysis of the TCR beta variable gene repertoire in chimpanzees: identification of functional homologs to human pseudogenes.

Chimpanzees are used for a variety of disease models such as hepatitis C virus (HCV) infection, where Ag-specific T cells are thought to be critical for resolution of infection. The variable segments of the TCR alphabeta genes are polymorphic and contain putative binding sites for MHC class I and II molecules. In this study, we performed a comprehensive analysis of genes that comprise the TCR beta variable gene (TCRBV) repertoire of the common chimpanzee Pan troglodytes. We identified 42 P. troglodytes TCRBV sequences representative of 25 known human TCRBV families. BV5, BV6, and BV7 are multigene TCRBV families in humans and homologs of most family members were found in the chimpanzee TCRBV repertoire. Some of the chimpanzee TCRBV sequences were identical with their human counterparts at the amino acid level. Notably four successfully rearranged TCRBV sequences in the chimpanzees corresponded to human pseudogenes. One of these TCR sequences was used by a cell line directed against a viral CTL epitope in an HCV-infected animal indicating the functionality of this V region in the context of immune defense against pathogens. These data indicate that some TCRBV genes maintained in the chimpanzee have been lost in humans within a brief evolutionary time frame despite remarkable conservation of the chimpanzee and human TCRBV repertoires. Our results predict that the diversity of TCR clonotypes responding to pathogens like HCV will be very similar in both species and will facilitate a molecular dissection of the immune response in chimpanzee models of human diseases.

Amino Acid Sequence↗

Isoenzyme diversity in Pneumocystis carinii from rats, mice, and rabbits.

Pneumocystis carinii is an opportunistic pathogen that causes pneumonia in immunocompromised patients. To investigate the genetic diversity of P. carinii populations, multilocus enzyme electrophoresis was used to analyze five enzyme systems (malate dehydrogenase, glucose phosphate isomerase, leucine aminopeptidase, malic enzyme, and 6-phosphogluconate dehydrogenase). Only five different multilocus associations (zymodemes) were recorded for the 70 isolates studied. While only one multilocus combination was found in mice and rabbits, three different multilocus associations were recorded in rats. Population genetic tests and phylogenetic analysis strongly suggest that P. carinii genotypes are host-specific, in agreement with molecular study results, and that no genetic exchange occurs between genotypes from different host species. This hypothesis could be verified only by the evolutionary genetic approach, which relies here on multilocus analysis.

Animals↗

The complexity of genetic variation in a simple immune system.

Fruitflies derived from a wild population vary in their resistance to infection with the bacterial pathogen Serratia marcescens. A survey of nucleotide diversity in 21 genes involved in innate immunity concluded that 16 genes had polymorphisms associated with resistance to this specific pathogen. However, the effects of individual polymorphisms on the resistance phenotype were modest, and epistatic interactions appeared to be common. What might these findings tell us about genetic resistance to infection in humans?

Animals↗