Amarisolide F, an Acylated Diterpenoid Glucoside and Related Terpenoids from Salvia amarissima.

Nine terpenoids were isolated from the leaves and flowers of Salvia amarissima, including a new acylated diterpenoid glucoside, amarisolide F (1), a new neo-clerodane diterpenoid, amarissinin D (2), which was isolated as an acetyl derivative (2a), and four known diterpenoids. The structure of amarisolide F (1) was elucidated by NMR and MS data analyses, as well as its methanolysis products 7 and 8, which also constituted new diterpenoids, named amarissinin E and 8- epi-amarissinin E, respectively. The absolute configuration of compound 7 was established by single-crystal X-ray diffraction. The cytotoxicity and anti-MDR effect of 1 in three phenotypes of the MCF-7 cell lines were assayed. Compound 1 was 2-3.6-fold more active than amarissinins A (3) and B (4), but several orders of magnitude less active than teotihuacanin (6) and reserpine.

Engineering and expression of a RhoA peptide against respiratory syncytial virus infection in plants.

MAIN CONCLUSION : A RhoA-derived peptide fused to carrier molecules from plants showed enhanced biological activity of in vitro assays against respiratory syncytial virus compared to the RhoA peptide alone or the synthetic RhoA peptide. A RhoA-derived peptide has been reported for over a decade as a potential inhibitor of respiratory syncytial virus (RSV) infection both in vitro and in vivo and is anticipated to be a promising alternative to monoclonal antibody-based therapy against RSV infection. However, there are several challenges to furthering development of this antiviral peptide, including improvement in the peptide's bioavailability, development of an efficient delivery system and identification of a cost-effective production platform. In this study, we have engineered a RhoA peptide as a genetic fusion to two carrier molecules, either lichenase (LicKM) or the coat protein (CP) of Alfalfa mosaic virus. These constructs were introduced into Nicotiana benthamiana plants using a tobacco mosaic virus-based expression vector and targets purified. The results demonstrated that the RhoA peptide fusion proteins were efficiently expressed in N. benthamiana plants, and that two of the resulting fusion proteins, RhoA-LicKM and RhoA2-FL-d25CP, inhibited RSV growth in vitro by 50 and 80 %, respectively. These data indicate the feasibility of transient expression of this biologically active antiviral RhoA peptide in plants and the advantage of using a carrier molecule to enhance target expression and efficacy.

HRA2pl peptide: a fusion inhibitor for human metapneumovirus produced in tobacco plants by transient transformation.

MAIN CONCLUSION: The HRA2pl peptide expressed by transient transformation in N. tabacum plants is capable of inhibiting the binding of the human metapneumovirus to HEp-2 cells at the fusion stage. Human metapneumovirus (hMPV) is an agent responsible for acute respiratory infections that mainly affects children under 3 years, the elderly and immunocompromised patients. In children younger than 5 years, respiratory tract infections account for 20 % of deaths worldwide. However, there is currently no treatment or vaccine available against hMPV. The production of a safe, efficient and low cost treatment against this virus is a current challenge. Plants provide a system for recombinant protein production that is cost effective and is easier to scale up to an industrial level than other platforms; in addition, the plant tissue may be used as raw food, dried or, alternatively, proteins may be partially or fully purified and administered in aerosol or capsules as dry powder. In this study, we designed a gene expressing an antiviral peptide against hMPV based on the heptad repeat A domain of the F protein of the virus. We produced the recombinant peptide by a viral transient expression system (Magnifection(®)) in Nicotiana tabacum plants. The efficacy of this antiviral peptide was confirmed by in vitro assays in HEp-2 cell line. This is a promising result that can offer a prophylactic approach against hMPV.

A chloroplast-derived C4V3 polypeptide from the human immunodeficiency virus (HIV) is orally immunogenic in mice.

Although the human immunodeficiency virus (HIV) causes one of the most important infectious diseases worldwide, attempts to develop an effective vaccine remain elusive. Designing recombinant proteins capable of eliciting significant and protective mammalian immune responses remain a priority. Moreover, large-scale production of proteins of interest at affordable cost remains a challenge for modern biotechnology. In this study, a synthetic gene encoding a C4V3 recombinant protein, known to induce systemic and mucosal immune responses in mammalian systems, has been introduced into tobacco chloroplasts to yield high levels of expression. Integration of the transgene into the tobacco plastome has been verified by Southern blot hybridization. The recombinant C4V3 protein is also detected in tobacco chloroplasts by confocal microscopy. Reactivity of the heterologous protein with both an anti-C4V3 rabbit serum as well as sera from HIV positive patients have been assayed using Western blots. When administered by the oral route in a four-weekly dose immunization scheme, the plant-derived C4V3 has elicited both systemic and mucosal antibody responses in BALB/c mice, as well as CD4+ T cell proliferation responses. These findings support the viability of using plant chloroplasts as biofactories for HIV candidate vaccines, and could serve as important vehicles for the development of a plant-based candidate vaccine against HIV.

Distribution of CO(2) fixation and acetate mineralization pathways in microorganisms from extremophilic anaerobic biotopes.

Extremophilic anaerobes are widespread in saline, acid, alkaline, and high or low temperature environments. Carbon is essential to living organisms and its fixation, degradation, or mineralization is driven by, up to now, six metabolic pathways. Organisms using these metabolisms are known as autotrophs, acetotrophs or carbon mineralizers, respectively. In anoxic and extreme environments, besides the well-studied Calvin-Benson-Bassham cycle, there are other five carbon fixation pathways responsible of autotrophy. Moreover, regarding carbon mineralization, two pathways perform this key process for carbon cycling. We might imagine that all the pathways can be found evenly distributed in microbial biotopes; however, in extreme environments, this does not occur. This manuscript reviews the most commonly reported anaerobic organisms that fix carbon and mineralize acetate in extreme anoxic habitats. Additionally, an inventory of autotrophic extremophiles by biotope is presented.

Oral immunogenicity of tomato-derived sDPT polypeptide containing Corynebacterium diphtheriae, Bordetella pertussis and Clostridium tetani exotoxin epitopes.

DPT vaccine, designed to immunize against diphtheria, pertussis, and tetanus, has been shown to be effective in humans. Nevertheless, dissatisfaction with the whole-cell preparations is due to the reactogenicity, which has to lead to the development of new safer formulations. Previously, we described the expression in tomato of a plant-optimized synthetic gene encoding the recombinant polypeptide sDPT, containing mainly immunoprotective epitopes of the diphtheria, pertussis and tetanus exotoxins and two adjuvants. In this study, we examined whether the ingestion of tomato-derived sDPT protein induces specific antibodies in mice after three weekly doses scheme. A positive group immunized with DPT toxoids was included. Specific antibody levels were assessed in serum, gut and lung. Sera tested for IgG antibody response to pertussis, tetanus and diphtheria toxin showed responses to the foreign antigens; interestingly, the response to diphtheria epitope was similar to those observed in the positive group. We found higher IgG1 than IgG2a responses in serum. A modest IgG response was observed in the tracheopulmonary fluid. High response of IgA against tetanus toxin was evident in gut, which was statistically comparable to that obtained in the positive group. The levels of response in these groups were higher than those in mice that received wild-type tomato. These findings support the concept of using transgenic tomatoes expressing sDPT polypeptide as model for edible vaccine against diphtheria, pertussis, and tetanus.

Immunogenicity of nuclear-encoded LTB:ST fusion protein from Escherichia coli expressed in tobacco plants.

Enterotoxigenic Escherichia coli (ETEC) is one of the main causative agents of diarrhea in infants and for travelers. Inclusion of a heat-stable (ST) toxin into vaccine formulations is mandatory as most ETEC strains can produce both heat-labile (LT) and ST enterotoxins. In this study, a genetic fusion gene encoding for an LTB:ST protein has been constructed and transferred into tobacco via Agrobacterium tumefaciens-mediated transformation. Transgenic tobacco plants carrying the LTB:ST gene are then subjected to GM1-ELISA revealing that the LTB:ST has assembled into pentamers and displays antigenic determinants from both LTB and ST. Protein accumulation of up to 0.05% total soluble protein is detected. Subsequently, mucosal and systemic humoral responses are elicited in mice orally dosed with transgenic tobacco leaves. This has suggested that the plant-derived LTB:ST is immunogenic via the oral route. These findings are critical for the development of a plant-based vaccine capable of eliciting broader protection against ETEC and targeting both LTB and ST. Features of this platform in comparison to transplastomic approaches are discussed.

Comparative RNA-Seq Analysis Reveals Potentially Resistance-Related Genes in Response to Bacterial Canker of Tomato.

Tomato is one of the most important crops for human consumption. Its production is affected by the actinomycete Clavibacter michiganensis subsp. michiganensis (Cmm), one of the most devastating bacterial pathogens of this crop. Several wild tomato species represent a source of natural resistance to Cmm. Here, we contrasted the transcriptomes of the resistant wild tomato species Solanum arcanum LA2157 and the susceptible species Solanum lycopersicum cv. Ailsa Craig, during the first 24 h of challenge with Cmm. We used three analyses approaches which demonstrated to be complementary: mapping to S. lycopersicum reference genome SL3.0; semi de novo transcriptome assembly; and de novo transcriptome assembly. In a global context, transcriptional changes seem to be similar between both species, although there are some specific genes only upregulated in S. arcanum during Cmm interaction, suggesting that the resistance regulatory mechanism probably diverged during the domestication process. Although S. lycopersicum showed enriched functional groups related to defense, S. arcanum displayed a higher number of induced genes related to bacterial, oomycete, and fungal defense at the first few hours of interaction. This study revealed genes that may contribute to the resistance phenotype in the wild tomato species, such as those that encode for a polyphenol oxidase E, diacyl glycerol kinase, TOM1-like protein 6, and an ankyrin repeat-containing protein, among others. This work will contribute to a better understanding of the defense mechanism against Cmm, and the development of new control methods.

The nutrient-improvement bacteria selected by Agave lechuguilla T. and their role in the rhizosphere community.

Agave lechuguilla has one of the widest distributions among other agave species in the Chihuahuan Desert. Their capacity to grow in poorly developed soils and harsh conditions has been related to their association with plant growth-promoting rhizobacteria. In this work, we explored how soil properties and plant growth stage influence the composition of the rhizobacterial communities, their interactions, and the enzymatic activity and abundance of nitrogen-fixing bacteria and organic phosphorus-mineralizing bacteria in two subregions of the Chihuahuan Desert. We found that mature plants of lechuguilla stimulated the activity and abundance of nutrient-improvement rhizobacteria, and these soil samples had a higher content of total organic carbon, ammonium (NH4) and nitrite + nitrate (NO2+NO3). Nutrient availability seems to be an essential driver of the bacterial community's structure since the genera with more connections (hubs) were those with known mechanisms related to the availability of nutrients, such as env. OPS17 (Bacteroidetes), Gemmatimonadaceae uncultured, S0134terrestrial group, BD211terrestrial group (Gemmatimonadetes), Chthoniobacteracea and Candidatus Udaeobacter (Verrucomicrobia). This work shows that the late growth stages of lechuguilla recruit beneficial bacteria that favor its establishment and tolerance to harsh conditions of the arid lands.

Antibodies induced by oral immunization of mice with a recombinant protein produced in tobacco plants harboring Bordetella pertussis epitopes.

Bordetella pertusis causes whooping cough or pertussis, disease that has not been eradicated and is reemerging despite the availability and massive application for decades of vaccines, such as Boostrix® which is an acellular vaccine harboring two regions of S1 subunit of the pertussis toxin, one region of filamentous hemagglutinin and one region of pertactin. In 2008, the World Health Organization estimated 16 million new cases and 95% occurred in developing countries with 195,000 children's deaths. We attempt to improve the vaccine against whooping cough and reduce its production costs by obtaining plants and bacteria expressing a heterologous protein harboring pertactin, pertussis toxin, and filamentous hemagglutinin epitopes from B. pertussis and assessing its immunogenicity after oral administration to mice. First, we designed a synthetic gene that encodes a multiepitope, then it was cloned into a vector for transient transformation by infiltration of tobacco plants with low amounts of nicotine; the codon bias-optimized construct was also cloned into an Escherichia coli expression vector. Recombinant proteins from E. coli cells (PTF) and tobacco leaves (PTF-M3') were purified by nickel affinity with a yield of 0.740 mg of recombinant protein per g dry weight. Purified recombinant proteins were administered orally to groups of Balb/c mice using the Boostrix® vaccine and vehicle (PBS) as positive and negative controls, respectively. A higher mucosal and systemic antibody responses were obtained in mice receiving the PTF and PTF-M3' proteins than Boostrix® or PBS. These findings prove the concept that oral administration of multiepitope recombinant proteins expressed in plants may be a potential edible vaccine. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11240-021-02107-1.

A Novel Isolate of Bacillus cereus Promotes Growth in Tomato and Inhibits Clavibacter michiganensis Infection under Greenhouse Conditions.

The need to produce food in a sustainable way to counteract the effects of excessive use of agrochemicals opens the door to the generation of new technologies that are not based on fossil fuels and are less toxic to ecosystems. Plant growth-promoting bacteria (PGPB) could represent an alternative to chemical biofertilizers and pesticides offering protection for biotic and abiotic stresses. In this work, a bacterial isolate from roots of castor bean (Ricinus communis) was identified and named as Bacillus cereus strain "Amazcala" (B.c-A). This isolate displayed the ability to solubilize inorganic phosphate and produce gibberellic acid (GA3). Moreover, this bacterium provided significant increases in height, stem width, dry weight, and total chlorophyll content in tomato plants. Interestingly, B.c-A also significantly decreased the severity of bacterial canker disease on tomato caused by Clavibacter michiganensis (Cmm) in preventive disease assays under greenhouse conditions. Based on our results, B.c-A can be considered as PGPB and a useful tool in Cmm disease control on tomato plant under greenhouse conditions.

Influence of adjuvants on the amount, specificity and functional activity of antibody response to human influenza vaccine in mice.

It's been almost a century since immunologists started using adjuvants as tools to develop more effective vaccines. Despite the rising number of adjuvanted vaccines in the last decades, we still lack knowledge of the adjuvants' effects on antibody response. This study was aimed to test the effect of immunizing mice with the human Inactivated Influenza vaccine (IIV), either alone or combined with different widely used adjuvants on the specific antibody response induced. Differential levels of IgM and IgG subclasses were found with the different adjuvants tested. Higher levels of antibodies did not always correspond with a higher efficacy to interfere with the virus infectivity. Differences in neutralization properties are possibly mediated by the specificity of the repertoire of antibodies induced. The repertoire was studied using a phage display 7-mer peptide library to screen for epitopes/mimotopes recognized by serum pools from vaccinated mice. The selected phage clones included peptides that corresponded to conformational mimotopes since they have no homology with lineal sequences of the Influenza strains' proteins. Five peptides were identified as recognized by sera from mice immunized with the IIV vaccine alone, including peptides from the hemagglutinin stalk domain, and by sera from mice immunized with the vaccine plus the different adjuvants employed. Adjuvants elicited a more diverse repertoire of epitope-recognizing antibodies that recognized epitopes of the HA recombinant globular head. Mimotopes were theoretically located at the neutralizing antigenic sites of the globular head of Influenza A H1N1pdm09, Influenza A H3N2, and Influenza B hemagglutinin. This study illustrates how different adjuvants can modify the extent and quality of humoral immunity against the IIV vaccine and the effectiveness of vaccination.

Expression of an immunogenic F1-V fusion protein in lettuce as a plant-based vaccine against plague.

Yersinia pestis is a pathogenic agent that causes the bubonic and pneumonic plague. The development of an efficient and low-cost oral vaccine against these diseases is highly desirable. In this study, the immunogenic fusion protein F1-V from Y. pestis was introduced into lettuce via Agrobacterium-mediated transformation, and putative transgenic lines were developed. The presence of the transgene in these putative transgenic lines was determined using polymerase chain reaction (PCR), and transgene integration and transgene copy number were confirmed following Southern blot analysis. The presence of specific F1-V transcripts was confirmed by reverse-transcriptase (RT)-PCR. Using monoclonal antibodies, ELISA and western blot analysis revealed that the expected antigenic F1-V protein was successfully expressed in transgenic lines. Mice immunized subcutaneously with lettuce expressing the F1-V antigen developed systemic humoral responses as 'proof of concept' of using lettuce as a production platform for the F1-V immunogen that could be used as a candidate plant-based vaccine against plague.

Analysis of a new strain of Euphorbia mosaic virus with distinct replication specificity unveils a lineage of begomoviruses with short Rep sequences in the DNA-B intergenic region.

BACKGROUND: Euphorbia mosaic virus (EuMV) is a member of the SLCV clade, a lineage of New World begomoviruses that display distinctive features in their replication-associated protein (Rep) and virion-strand replication origin. The first entirely characterized EuMV isolate is native from Yucatan Peninsula, Mexico; subsequently, EuMV was detected in weeds and pepper plants from another region of Mexico, and partial DNA-A sequences revealed significant differences in their putative replication specificity determinants with respect to EuMV-YP. This study was aimed to investigate the replication compatibility between two EuMV isolates from the same country. RESULTS: A new isolate of EuMV was obtained from pepper plants collected at Jalisco, Mexico. Full-length clones of both genomic components of EuMV-Jal were biolistically inoculated into plants of three different species, which developed symptoms indistinguishable from those induced by EuMV-YP. Pseudorecombination experiments with EuMV-Jal and EuMV-YP genomic components demonstrated that these viruses do not form infectious reassortants in Nicotiana benthamiana, presumably because of Rep-iteron incompatibility. Sequence analysis of the EuMV-Jal DNA-B intergenic region (IR) led to the unexpected discovery of a 35-nt-long sequence that is identical to a segment of the rep gene in the cognate viral DNA-A. Similar short rep sequences ranging from 35- to 51-nt in length were identified in all EuMV isolates and in three distinct viruses from South America related to EuMV. These short rep sequences in the DNA-B IR are positioned downstream to a ~160-nt non-coding domain highly similar to the CP promoter of begomoviruses belonging to the SLCV clade. CONCLUSIONS: EuMV strains are not compatible in replication, indicating that this begomovirus species probably is not a replicating lineage in nature. The genomic analysis of EuMV-Jal led to the discovery of a subgroup of SLCV clade viruses that contain in the non-coding region of their DNA-B component, short rep gene sequences located downstream to a CP-promoter-like domain. This assemblage of DNA-A-related sequences within the DNA-B IR is reminiscent of polyomavirus microRNAs and could be involved in the posttranscriptional regulation of the cognate viral rep gene, an intriguing possibility that should be experimentally explored.

Expression of a multi-epitope DPT fusion protein in transplastomic tobacco plants retains both antigenicity and immunogenicity of all three components of the functional oligomer.

Expression of genes in plant chloroplasts provides an opportunity for enhanced production of target proteins. We report the introduction and expression of a fusion DPT protein containing immunoprotective exotoxin epitopes of Corynebacterium diphtheriae, Bordetella pertussis, and Clostridium tetani in tobacco chloroplasts. Using biolistic-mediated transformation, a plant-optimized synthetic DPT gene was successfully transferred to tobacco plastomes. Putative transplastomic T0 plants were identified by PCR, and Southern blot analysis confirmed homoplasmy in T1 progeny. ELISA assays demonstrated that the DPT protein retained antigenicity of the three components of the fusion protein. The highest level of expression in these transplastomic plants reached 0.8% of total soluble protein. To assess whether the functional recombinant protein expressed in tobacco plants would induce specific antibodies in test animals, a mice feeding experiment was conducted. For mice orally immunized with freeze-dried transplastomic leaves, production of IgG and IgA antibodies specific to each toxin were detected in serum and mucosal tissues.

Characterization of sulfate-reducing bacteria dominated surface communities during start-up of a down-flow fluidized bed reactor.

An anaerobic down-flow fluidized bed reactor was inoculated with granular sludge and started-up with sulfate containing synthetic wastewater to promote the formation of a biofilm enriched in sulfate-reducing bacteria (SRB), to produce biogenic sulfide. The start-up was done in two stages operating the reactor in batch for 45 days followed by 85 days of continuous operation. Low-density polyethylene was used as support. The biofilm formation was followed up by biochemical and electron microscopy analyses and the composition of the community was examined by 16S rDNA sequence analysis. Maximum immobilized volatile solids (1.2 g IVS/L(support)) were obtained after 14 days in batch regime. During the 85 days of continuous operation, the reactor removed up to 80% of chemical oxygen demand (COD), up to 28% of the supplied sulfate and acetate was present in the effluent. Sulfate-reducing activity determined in the biofilm with ethanol or lactate as substrate was 11.7 and 15.3 g COD/g IVS per day, respectively. These results suggested the immobilization of sulfate reducers that incompletely oxidize the substrate to acetate; the phylogenetic analysis of the cloned 16S rDNA gene sequences showed high identity to the genus Desulfovibrio that oxidizes the substrates incompletely. In contrast, in the granular sludge used as inoculum a considerable number of clones showed homology to Methanobacterium and just few clones were close to SRB. The starting-up approach allowed the enrichment of SRB within the diverse community developed over the polyethylene support.

Effect of an infection control program on the frequency of nosocomial viral respiratory infections.

We determined the rate of nosocomial viral respiratory infection in infants and the effect of an infection control program during 4 winter seasons. The rate of nosocomial viral respiratory infection decreased from 6.09 episodes per 100 patients admitted during the first study year to 1.46 episodes per 100 patients admitted during the last study year.

Antitumor and immunostimulatory activities of a genotype V recombinant attenuated veterinary Newcastle disease virus vaccine.

Antitumor conventional treatments including chemo/radiotherapy result in several side effects and non-specificity. Therapies including the use of oncolytic viruses, particularly the Newcastle disease virus (NDV), have emerged as an attractive alternative due to their capacity to kill cancer cells directly or through stimulation of the immune system. In the present study, a commercial vaccine composed of a recombinant attenuated NDV strain P05 (rNDV-P05) was assessed for antitumor and immunostimulatory activity. Firstly, hemagglutination activity was evaluated at different pH and temperature conditions. Then, cancer cell lines and peripheral blood mononuclear cells (PBMC) were co-cultured with or without rNDV-P05 and cytoplasmic nucleosomes were measured by enzyme-linked immunosorbent assay (ELISA) as an apoptosis indicator. Antitumor cytokines produced by PBMC in response to the virus were analyzed by ELISA and reverse transcription quantitative polymerase chain reaction. Characterization of rNDV-P05 indicates that the virus is slightly sensible to acid and basic pH, and stable at temperatures no greater than 42°C. The majority of cell lines developed apoptosis in co-culture with rNDV-P05 in a dose-time dependent manner. The highest level of HeLa, HCC1954 and HepG2 cell apoptosis was at 48 h/50 hemagglutination units (HU), and HL-60 was 24 h/50 HU. A549 cell line and PBMC did not show sensitivity to apoptosis by the virus. PBMC from healthy donors stimulated with the rNDV-P05 increased significantly the levels of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α and soluble TNF-related apoptosis-inducing ligand in culture supernatants, as well as their mRNA expression. These results demonstrate that the pro-apoptotic effect of rNDV-P05 and its magnitude is specific to particular tumor cell lines and is not induced on PBMC; and the virus stimulates the expression of several key antitumor cytokines. This study promotes the use of rNDV-P05 in an alternate application of different viral strains during virotherapy with NDV.

Human metapneumovirus infections in Mexico: epidemiological and clinical characteristics.

The human metapneumovirus (hMPV) is a recently described respiratory RNA virus that mainly affects children. To date there has not been a report that describes the detection of this virus in Mexico. This study was performed to detect hMPV in hospitalized Mexican children with respiratory infections, and describe their epidemiological and clinical characteristics. Nasal wash samples from 558 children younger than 3 years of age with the admission diagnosis of a respiratory tract infection were evaluated. Respiratory viruses were detected in 221 children [respiratory syncytial virus (RSV), 193 (34.6 %); influenza virus, 13 (2.3 %); parainfluenza viruses, 15 (2.7 %)]. Respiratory secretions of 323 children in whom the presence of these viruses was excluded (131 admitted during the 2002-2003 respiratory season and 192 during the 2003-2004 season) were tested for hMPV infection. The hMPV genome was detected in 34 specimens by amplification using real-time RT-PCR. Sequencing of amplicons and phylogenetic analysis indicated the predominance of genotype A hMPV. The months with the highest number of hMPV detections were February and March. During the 2002-2003 season hMPV activity peaked after the RSV season. During the 2003-2004 season hMPV and RSV epidemics occurred simultaneously. The clinical presentation of an hMPV infection was indistinguishable from other respiratory infections. Except for one death, the outcomes of the hMPV infections were good. In this study, among the viruses routinely tested for, hMPV was the second most common agent, after RSV, in children younger than 3 years of age hospitalized with respiratory tract infections.

Metapneumovirus humano: epidemiología y posibles tratamientos profilácticos / Human Metapneumovirus: Epidemiology and Possible Prophylactic Treatments

Resumen En el 2001, se identificó en Holanda al metapneumovirus humano (hMPV) como un "nuevo" agente etiológico causante de infecciones respiratorias agudas en infantes menores de 5 años; sin embargo, también se ha aislado en personas de la tercera edad e inmunocomprometidos. Este virus se considera como el segundo agente etiológico en enfermedades agudas del tracto respiratorio. En la actualidad, el costo estimado de las infecciones respiratorias agudas (IRA) en nuestro país es de 9,000 dólares estadounidenses por paciente hospitalizado. El hMPV es un miembro del género Metapneumovirus, familia Pneumoviridae, que pertenece al orden de los Mononegavirales, correspondiente a virus de ácido ribonucleico (RNA) monocatenario negativo, que consta de 8 genes en el orden 3'-N-P-M-F-M2-SH-G-L-5', y que codifica para 9 proteínas. De estas proteínas, la glicoproteína de fusión F está altamente conservada en el género Metapneumovirus y es el mayor determinante antigénico, y al no existir aún vacuna aprobada para este virus, se ha utilizado como un epítopo candidato para el diseño de una vacuna que confiera inmunidad al hospedero o como un blanco terapéutico en la creación de péptidos antivirales que inhiban la fusión del virus a su célula blanco y se evite la infección en sujetos de alto riesgo de contagio, ya que en la actualidad no se ha aprobado por la COFEPRIS ningún tratamiento profiláctico contra hMPV.

Abstract In 2001 in the Netherlands, Human metapneumovirus (hMPV) was identified as a "new" etiologic agent causing acute respiratory infections in children younger than 5 years old; however, it has also been isolated in the elderly and immunocompromised people. This virus is considered the second etiological agent in acute diseases of the respiratory tract. Currently, the estimated cost of IRAs in our country is of 9,000 USD per inpatient. hMPV is a member of the genus Metapneumovirus, family Pneumoviridae, and it belongs to the order Mononegavirales that is part of the negative single-stranded ribonucleic acid (RNA) virus, consisting of eight genes ordered: 3'-N-P-M-F-M2-SH-G-L-5 ', and which encodes for 9 proteins. Of these proteins, the F fusion glycoprotein is highly conserved in the genus Metapneumovirus, and is the major antigenic determinant, and because an approved vaccine doesn't exist, it has been used as a candidate epitope for the design of a vaccine that confers host immunity or as a therapeutic target in the creation of antiviral peptides that inhibit the fusion of the virus to its target cell and to avoid infection in subjects at high risk of contagion since there is currently none accepted by COFEPRIS as a prophylactic treatment against hMPV.