RESUMEN
The causative agent of COVID-19 pandemic, SARS-CoV-2, has a 29,903 bases positive-sense single-stranded RNA genome. RNAs exhibit about 150 modified bases that are essential for proper function. Among internal modified bases, the N6-methyladenosine, or m6A, is the most frequent, and is implicated in SARS-CoV-2 immune response evasion. Although the SARS-CoV-2 genome is RNA, almost all genomes sequenced thus far are, in fact, reverse transcribed complementary DNAs. This process reduces the true complexity of these viral genomes because the incorporation of dNTPs hides RNA base modifications. Here, we present an initial exploration of Nanopore direct RNA sequencing to assess the m6A residues in the SARS-CoV-2 sequences of ORF3a, E, M, ORF6, ORF7a, ORF7b, ORF8, N, ORF10 and the 3'-untranslated region. We identified fifteen m6A methylated positions, of which, six are in ORF N. Additionally, because m6A is associated with the DRACH motif, we compared its distribution in major SARS-CoV-2 variants. Although DRACH is highly conserved among variants, we show that variants Beta and Eta have a fourth position C > U change in DRACH at 28,884b that could affect methylation. This is the first report of direct RNA sequencing of a Brazilian SARS-CoV-2 sample coupled with the identification of modified bases.
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Adenosina/análogos & derivados , COVID-19/virología , Evasión Inmune/genética , ARN Viral/metabolismo , SARS-CoV-2/genética , Regiones no Traducidas 3' , Adenosina/metabolismo , Animales , Chlorocebus aethiops , Genoma Viral , Humanos , Metilación , Secuenciación de Nanoporos/métodos , Sistemas de Lectura Abierta , Análisis de Secuencia de ARN/métodos , Células VeroRESUMEN
SARS-CoV-2 VOC immune evasion is mainly due to lower cross-reactivity from previously elicited class I/II neutralizing antibodies, while increased affinity to hACE2 plays a minor role. The affinity between antibodies and VOCs is impacted by remodeling of the electrostatic surface potential of the Spike RBDs. The P.3 variant is a putative VOC.
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Anticuerpos Neutralizantes/inmunología , Afinidad de Anticuerpos/genética , Evasión Inmune/genética , SARS-CoV-2/inmunología , Afinidad de Anticuerpos/inmunología , Reacciones Cruzadas/genética , Modelos Moleculares , Dominios Proteicos , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/inmunología , Electricidad EstáticaRESUMEN
BACKGROUND: Human immunodeficiency virus (HIV-1) infection is characterized by high viral replication and a decrease in CD4+ T cells (CD4+TC), resulting in AIDS, which can lead to death. In elite controllers and viremia controllers, viral replication is naturally controlled, with maintenance of CD4+TC levels without the use of antiretroviral therapy (ART). METHODS: The aim of the present study was to describe virological and immunological risk factors among HIV-1-infected individuals according to characteristics of progression to AIDS. The sample included 30 treatment-naive patients classified into three groups based on infection duration (> 6 years), CD4+TC count and viral load: (i) 2 elite controllers (ECs), (ii) 7 viremia controllers (VCs) and (iii) 21 nonviremia controllers (NVCs). Nested PCR was employed to amplify the virus genome, which was later sequenced using the Ion PGM platform for subtyping and analysis of immune escape mutations. RESULTS: Viral samples were classified as HIV-1 subtypes B and F. Greater selection pressure on mutations was observed in the group of viremia controllers, with a higher frequency of immunological escape mutations in the genes investigated, including two new mutations in gag. The viral sequences of viremia controllers and nonviremia controllers did not differ significantly regarding the presence of immune escape mutations. CONCLUSION: The results suggest that progression to AIDS is not dependent on a single variable but rather on a set of characteristics and pressures exerted by virus biology and interactions with immunogenetic host factors.
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Síndrome de Inmunodeficiencia Adquirida/inmunología , VIH-1/genética , Evasión Inmune/genética , Mutación/inmunología , Síndrome de Inmunodeficiencia Adquirida/virología , Adulto , Brasil , Linfocitos T CD4-Positivos/inmunología , Estudios Transversales , Femenino , Genes gag/genética , Humanos , Masculino , Filogenia , Conformación Proteica , Estudios Retrospectivos , Carga Viral , Viremia/genética , Replicación Viral/genética , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/química , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/genéticaRESUMEN
Due to the scope and impact of the COVID-19 pandemic there exists a strong desire to understand where the SARS-CoV-2 virus came from and how it jumped species boundaries to humans. Molecular evolutionary analyses can trace viral origins by establishing relatedness and divergence times of viruses and identifying past selective pressures. However, we must uphold rigorous standards of inference and interpretation on this topic because of the ramifications of being wrong. Here, we dispute the conclusions of Xia (2020. Extreme genomic CpG deficiency in SARS-CoV-2 and evasion of host antiviral defense. Mol Biol Evol. doi:10.1093/molbev/masa095) that dogs are a likely intermediate host of a SARS-CoV-2 ancestor. We highlight major flaws in Xia's inference process and his analysis of CpG deficiencies, and conclude that there is no direct evidence for the role of dogs as intermediate hosts. Bats and pangolins currently have the greatest support as ancestral hosts of SARS-CoV-2, with the strong caveat that sampling of wildlife species for coronaviruses has been limited.
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Alphacoronavirus/genética , Betacoronavirus/genética , Infecciones por Coronavirus/epidemiología , Genoma Viral , Pandemias , Neumonía Viral/epidemiología , Virus Reordenados/genética , Alphacoronavirus/clasificación , Alphacoronavirus/patogenicidad , Animales , Betacoronavirus/clasificación , Betacoronavirus/patogenicidad , Evolución Biológica , COVID-19 , Quirópteros/virología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Islas de CpG , Perros , Euterios/virología , Humanos , Evasión Inmune/genética , Neumonía Viral/inmunología , Neumonía Viral/transmisión , Neumonía Viral/virología , Unión Proteica , ARN Viral/genética , ARN Viral/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/inmunología , Proteínas de Unión al ARN/metabolismo , Virus Reordenados/clasificación , Virus Reordenados/patogenicidad , SARS-CoV-2 , Replicación ViralRESUMEN
INTRODUCTION AND OBJECTIVES: The hepatitis B virus (HBV) surface antigen (HBsAg) variations suggested having some effects on infection outcome. Due to some controversial issues, the aim of this study was to compare the pattern of HBsAg variation between asymptomatic carriers and HCC/cirrhosis patients. MATERIALS AND METHODS: In this cross-sectional study, 19 HCC/cirrhotic and 26 asymptomatic patients were enrolled. After viral DNA extraction, HBs gene was amplified using an in-house nested-PCR. Then, PCR products were introduced into bi-directional Sanger sequencing. The retrieved sequences were compared with references, to investigate the variation of immunologic sites, major hydrophilic region (MHR) of HBsAg as well as reverse transcriptase (RT), and also to determine genotype/subtype. RESULTS: The analysis of MHR and epitopes on HBsAg showed dozens of substitution, which occurred more prevalently in I110, P120, Y134, G159, S193, Y206, S207, I208, L213 and P214 positions. However, Y134N/F/L (P=0.04) and P120T/S (P=0.009) were significantly detected in MHR and B-cell epitope of HCC/Cirrhotic group. A number of truncation-related mutations were higher in HCC/Cirrhotic group (P>0.001), albeit only C69* stop codon was statistically significant (P=0.003). In RT, some potentially resistant substitutions such as Q215S, V191I and V214A, were revealed. Phylogenetic analysis showed that all of isolates belonged to genotype D, and the major serotype was ayw1. CONCLUSION: The higher frequency of substitutions in MHR and immune epitopes at positions such as Y134 and P120 as well as stop codons such as C69* in HCC/cirrhotic group might candidate them as predictive factors for infection outcome.
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Carcinoma Hepatocelular/virología , Portador Sano/virología , Farmacorresistencia Viral/genética , Productos del Gen pol/genética , Antígenos de Superficie de la Hepatitis B/genética , Hepatitis B Crónica/virología , Cirrosis Hepática/virología , Neoplasias Hepáticas/virología , Adulto , Infecciones Asintomáticas , ADN Viral/análisis , Epítopos de Linfocito B/genética , Epítopos de Linfocito T/genética , Femenino , Genotipo , Humanos , Evasión Inmune/genética , Masculino , Persona de Mediana Edad , Mutación , Adulto JovenRESUMEN
Several pathogens including Gram-negative bacteria hijack complement regulators to escape host's innate response. Pathogenic Leptospira species bind Factor H, C4b binding protein and vitronectin from the complement system. We evaluated the ability of low passage (LP) and culture-attenuated (CA) pathogenic strains of Leptospira, to bind Factor H. We used LOCaS46 (Leptospira interrogans sv Canicola), LOVe30 (L. interrogans sv Icterohaemorrhagiae) and MOCA45 (L. santarosai sv Tarassovi), and ten high passage strains of Leptospira [used in the microscopic agglutination test (MAT)]. Afterwards, we assessed their survival in normal human serum (NHS). Interestingly, the ability in binding Factor H was higher for LOCaS46 and LOVe30 LP strains, than for the respective CA strains suggesting that the ability of evading the alternative complement pathway is lost after culture attenuation. Accordingly, the level of mRNA expression of the Factor H binding proteins, LigA, LigB and Lsa23 was higher in these LP strains than in the corresponding CA strains. Unexpectedly, no difference in Factor H binding and surviving was observed between LP and CA MOCA45 strains. The high passage MAT-reference strains showed variation in Factor H binding ability, but, in most cases, the ability for capturing Factor H by Leptospira strains correlated with their survival in NHS.
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Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Proteínas Portadoras/metabolismo , Regulación Bacteriana de la Expresión Génica , Leptospira/inmunología , Leptospira/patogenicidad , Proteínas Portadoras/genética , Factor H de Complemento/metabolismo , Humanos , Evasión Inmune/genética , Leptospira/genética , Leptospirosis/microbiología , Viabilidad Microbiana/genética , Viabilidad Microbiana/inmunología , Unión Proteica , ARN Mensajero/genéticaRESUMEN
BACKGROUND: The leishmaniasis are parasitic diseases caused by protozoans of the genus Leishmania, highly divergent eukaryotes, characterized by unique biological features. To survive in both the mammalian hosts and insect vectors, these pathogens make use of a number of mechanisms, many of which are associated with parasite specific proteases. The metalloprotease GP63, the major Leishmania surface antigen, has been found to have multiple functions required for the parasite's survival. GP63 is encoded by multiple genes and their copy numbers vary considerably between different species and are increased in those from the subgenus Viannia, including L. braziliensis. RESULTS: By comparing multiple sequences from Leishmania and related organisms this study sought to characterize paralogs in silico, evaluating their differences and similarities and the implications for the GP63 function. The Leishmania GP63 genes are encoded on chromosomes 10, 28 and 31, with the genes from the latter two chromosomes more related to genes found in insect or plant parasites. Those from chromosome 10 have experienced independent expansions in numbers in Leishmania, especially in L. braziliensis. These could be clustered in three groups associated with different mRNA 3' untranslated regions as well as distinct C-terminal ends for the encoded proteins, with presumably distinct expression patterns and subcellular localizations. Sequence variations between the chromosome 10 genes were linked to intragenic recombination events, mapped to the external surface of the proteins and predicted to be immunogenic, implying a role against the host immune response. CONCLUSIONS: Our results suggest a greater role for the sequence variation found among the chromosome 10 GP63 genes, possibly related to the pathogenesis of L. braziliensis and closely related species within the mammalian host. They also indicate different functions associated to genes mapped to different chromosomes. For the chromosome 10 genes, variable subcellular localizations were found to be most likely associated with multiple functions and target substrates for this versatile protease.
Asunto(s)
Simulación por Computador , Variación Genética , Evasión Inmune/genética , Leishmania braziliensis/genética , Leishmania braziliensis/inmunología , Metaloendopeptidasas/genética , Secuencia de Aminoácidos , Cromosomas/genética , Epítopos de Linfocito B/inmunología , Evolución Molecular , Leishmania braziliensis/patogenicidad , Metaloendopeptidasas/química , Recombinación Genética , Homología de Secuencia de Ácido Nucleico , Virulencia/genéticaRESUMEN
Antigenic variation by variant surface glycoprotein (VSG) coat switching in African trypanosomes is one of the most elaborate immune evasion strategies found among pathogens. Changes in the identity of the transcribed VSG gene, which is always flanked by 70-bp and telomeric repeats, can be achieved either by transcriptional or DNA recombination mechanisms. The major route of VSG switching is DNA recombination, which occurs in the bloodstream VSG expression site (ES), a multigenic site transcribed by RNA polymerase I. Recombinogenic VSG switching is frequently catalyzed by homologous recombination (HR), a reaction normally triggered by DNA breaks. However, a clear understanding of how such breaks arise-including whether there is a dedicated and ES-focused mechanism-is lacking. Here, we synthesize data emerging from recent studies that have proposed a range of mechanisms that could generate these breaks: action of a nuclease or nucleases; repetitive DNA, most notably the 70-bp repeats, providing an intra-ES source of instability; DNA breaks derived from the VSG-adjacent telomere; DNA breaks arising from high transcription levels at the active ES; and DNA lesions arising from replication-transcription conflicts in the ES. We discuss the evidence that underpins these switch-initiation models and consider what features and mechanisms might be shared or might allow the models to be tested further. Evaluation of all these models highlights that we still have much to learn about the earliest acting step in VSG switching, which may have the greatest potential for therapeutic intervention in order to undermine the key reaction used by trypanosomes for their survival and propagation in the mammalian host.
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Trypanosoma/inmunología , Glicoproteínas Variantes de Superficie de Trypanosoma/genética , Glicoproteínas Variantes de Superficie de Trypanosoma/inmunología , Variación Antigénica/genética , Variación Antigénica/fisiología , ADN/metabolismo , Replicación del ADN/inmunología , Evasión Inmune/genética , Evasión Inmune/inmunología , Telómero/genética , Transcripción Genética/genética , Trypanosoma/genética , Trypanosoma brucei brucei/metabolismo , Tripanosomiasis Africana/genética , Tripanosomiasis Africana/inmunologíaRESUMEN
Pathogens have developed particular strategies to infect and invade their hosts. Amongst these strategies' figures the modulation of several components of the innate immune system participating in early host defenses, such as the coagulation and complement cascades, as well as the fibrinolytic system. The components of the coagulation cascade and the fibrinolytic system have been proposed to be interfered during host invasion and tissue migration of bacteria, fungi, protozoa, and more recently, helminths. One of the components that has been proposed to facilitate pathogen migration is plasminogen (Plg), a protein found in the host's plasma, which is activated into plasmin (Plm), a serine protease that degrades fibrin networks and promotes degradation of extracellular matrix (ECM), aiding maintenance of homeostasis. However, pathogens possess Plg-binding proteins that can activate it, therefore taking advantage of the fibrin degradation to facilitate establishment in their hosts. Emergence of Plg-binding proteins appears to have occurred in diverse infectious agents along evolutionary history of host-pathogen relationships. The goal of the present review is to list, summarize, and analyze different examples of Plg-binding proteins used by infectious agents to invade and establish in their hosts. Emphasis was placed on mechanisms used by helminth parasites, particularly taeniid cestodes, where enolase has been identified as a major Plg-binding and activating protein. A new picture is starting to arise about how this glycolytic enzyme could acquire an entirely new role as modulator of the innate immune system in the context of the host-parasite relationship.
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Proteínas Bacterianas/genética , Proteínas Portadoras/genética , Enfermedades Transmisibles/genética , Plasminógeno/genética , Enfermedades Transmisibles/microbiología , Enfermedades Transmisibles/patología , Matriz Extracelular/química , Matriz Extracelular/genética , Fibrina/genética , Fibrinolisina/genética , Fibrinólisis/genética , Interacciones Huésped-Patógeno/genética , Humanos , Evasión Inmune/genética , Inmunidad Innata/genética , ProteolisisRESUMEN
HIV circumvents HLA class I-restricted CD8+ T-cell responses through selection of escape mutations that leave characteristic mutational "footprints," also known as HLA-associated polymorphisms (HAPs), on HIV sequences at the population level. While many HLA footprints are universal across HIV subtypes and human populations, others can be region specific as a result of the unique immunogenetic background of each host population. Using a published probabilistic phylogenetically informed model, we compared HAPs in HIV Gag and Pol (PR-RT) in 1,612 subtype B-infected, antiretroviral treatment-naive individuals from Mexico and 1,641 individuals from Canada/United States. A total of 252 HLA class I allele subtypes were represented, including 140 observed in both cohorts, 67 unique to Mexico, and 45 unique to Canada/United States. At the predefined statistical threshold of a q value of <0.2, 358 HAPs (201 in Gag, 157 in PR-RT) were identified in Mexico, while 905 (534 in Gag and 371 in PR-RT) were identified in Canada/United States. HAPs identified in Mexico included both canonical HLA-associated escape pathways and novel associations, in particular with HLA alleles enriched in Amerindian and mestizo populations. Remarkably, HLA footprints on HIV in Mexico were not only fewer but also, on average, significantly weaker than those in Canada/United States, although some exceptions were noted. Moreover, exploratory analyses suggested that the weaker HLA footprint on HIV in Mexico may be due, at least in part, to weaker and/or less reproducible HLA-mediated immune pressures on HIV in this population. The implications of these differences for natural and vaccine-induced anti-HIV immunity merit further investigation.IMPORTANCE HLA footprints on HIV identify viral regions under intense and consistent pressure by HLA-restricted immune responses and the common mutational pathways that HIV uses to evade them. In particular, HLA footprints can identify novel immunogenic regions and/or epitopes targeted by understudied HLA alleles; moreover, comparative analyses across immunogenetically distinct populations can illuminate the extent to which HIV immunogenic regions and escape pathways are shared versus population-specific pathways, information which can in turn inform the design of universal or geographically tailored HIV vaccines. We compared HLA-associated footprints on HIV in two immunogenetically distinct North American populations, those of Mexico and Canada/United States. We identify both shared and population-specific pathways of HIV adaptation but also make the surprising observation that HLA footprints on HIV in Mexico overall are fewer and weaker than those in Canada/United States, raising the possibility that HLA-restricted antiviral immune responses in Mexico are weaker, and/or escape pathways somewhat less consistent, than those in other populations.
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Infecciones por VIH/genética , Infecciones por VIH/inmunología , VIH/inmunología , Antígenos HLA/genética , Antígenos HLA/inmunología , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/inmunología , Alelos , Secuencia de Aminoácidos , Canadá , Análisis por Conglomerados , Estudios de Cohortes , Frecuencia de los Genes , Antecedentes Genéticos , Variación Genética , Genética de Población , Infecciones por VIH/virología , Proteasa del VIH/genética , Proteasa del VIH/inmunología , Transcriptasa Inversa del VIH/genética , Transcriptasa Inversa del VIH/inmunología , Antígenos de Histocompatibilidad Clase I/genética , Antígenos de Histocompatibilidad Clase I/inmunología , Humanos , Evasión Inmune/genética , Fenómenos Inmunogenéticos , México , Mutación , Filogenia , Estados Unidos , Carga Viral , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/genética , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/inmunologíaRESUMEN
La actual epidemia de enfermedad por virus Ébola que azota al África Occidental ha cobrado la vida de alrededor de 9 000 personas con más de 22 000 infectados en seis países, y algunos casos aislados han llegado a ciudades de Europa y Estados Unidos. Aunque el curso clínico de la enfermedad es bien conocido, los mecanismos específicos que explican su patogenicidad no han sido completamente delineados. Los casos fatales de infección por Ébolavirus están marcados por un fallo catastrófico de las respuestas inmune innata y adaptativa, mediado por proteínas codificadas por el virus, así como por propiedades asociadas a su estructura. El genoma del Ébolavirus está constituido solamente por siete genes que codifican unas 10 proteínas, suficientes para desencadenar una enfermedad cuya letalidad varía del 40 al 90 por ciento. En el centro de la desregulación inducida por el Ébola se encuentra una temprana y coordinada actuación de las proteínas VP24, VP30 y VP35, que conduce a niveles elevados de replicación viral, a una inapropiada temporización de la cascada de liberación de linfocinas y a la muerte, tanto de células presentadoras de antígenos, como de células efectoras. Los complejos mecanismos del Ébola para regular selectivamente la respuesta inmune y su patogenicidad variable en diferentes especies hospederas, convierten a este virus en un adversario formidable, así como de un notable interés científico(AU)
The current Ebolavirus disease outbreak that strikes West Africa has claimed the life of around 9 000 people and has infected more than 22 000 in six countries, and some isolated cases have reached cities of Europe and the United States. Though the clinical course of the disease is well known, the specific mechanisms of its pathogenicity have not been fully delineated yet. Fatal cases of Ebolavirus disease are marked by a catastrophic failure of both innate and adaptive immune responses, mediated by virus-encoded proteins as well as properties associated with its structure. Ebolavirus genome comprises only seven genes encoding about 10 proteins, enough to cause a disease which fatality fluctuates from 40 to 90 percent. At the heart of Ebola-induced immune dysregulation is an early and coordinated disruption by VP24, VP30, and VP35 that leads to elevated levels of virus replication, a cascade of inappropriately timed cytokine release, and death of both antigen-presenting and responding immune cells. The complex mechanisms of Ebola to selectively regulate immune responses and its variable pathogenicity in different host species makes this virus both, a challenging foe and scientifically interesting(AU)
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Humanos , Biología Molecular/métodos , Patogenesia Homeopática/métodos , Evasión Inmune , Evasión Inmune/genéticaRESUMEN
The hepatitis B virus (HBV) infection is a public health problem worldwide. Considering HBV morbidity and mortality and the economic consequences .of this infection, policies and strategies to control it have been implemented, especially in regions where HBV infection is endemic, with high rates of vertical and horizontal infection. One of these strategies is the development of the recombinant vaccine. A 92% of the countries in the world have implemented the vaccine with a global coverage of 69%. The escape variants of HBV correspond to isolates with mutations in the sequence coding for the "a" determinant; these mutations result in changes in the amino acid sequence of the surface antigen (HBsAg) that prevent neutralization of viral particles by antibodies generated in response to vaccination or infection. The escape variants can infect vaccinated individuals and have been identified in the population of countries with different epidemiological patterns.
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Vacunas contra Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Hepatitis B/virología , Evasión Inmune/genética , Mutación/genética , ADN Viral/genética , Hepatitis B/inmunología , Hepatitis B/prevención & control , Anticuerpos contra la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Humanos , Inmunización PasivaAsunto(s)
Humanos , Vacunas contra Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Hepatitis B/virología , Evasión Inmune/genética , Mutación/genética , ADN Viral/genética , Anticuerpos contra la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Hepatitis B/inmunología , Hepatitis B/prevención & control , Inmunización PasivaRESUMEN
Proteins containing repetitive amino acid domains are widespread in all life forms. In parasitic organisms, proteins containing repeats play important roles such as cell adhesion and invasion and immune evasion. Therefore, extracellular and intracellular parasites are expected to be under different selective pressures regarding the repetitive content in their genomes. Here, we investigated whether there is a bias in the repetitive content found in the predicted proteomes of 6 exclusively extracellular and 17 obligate intracellular protozoan parasites, as well as 4 free-living protists. We also attempted to correlate the results with the distinct ecological niches they occupy and with distinct protein functions. We found that intracellular parasites have higher repetitive content in their proteomes than do extracellular parasites and free-living protists. In intracellular parasites, these repetitive proteins are located mainly at the parasite surface or are secreted and are enriched in amino acids known to be part of N- and O-glycosylation sites. Furthermore, in intracellular parasites, the developmental stages that are able to invade host cells express a higher proportion of proteins with perfect repeats relative to other life cycle stages, and these proteins have molecular functions associated with cell invasion. In contrast, in extracellular parasites, degenerate repetitive motifs are enriched in proteins that are likely to play roles in evading host immune response. Altogether, our results support the hypothesis that both the ability to invade host cells and to escape the host immune response may have shaped the expansion and maintenance of perfect and degenerate repeats in the genomes of intra- and extracellular parasites.