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1.
Nat Commun ; 12(1): 1607, 2021 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-33707453

RESUMEN

In recognizing the host cellular receptor and mediating fusion of virus and cell membranes, the spike (S) glycoprotein of coronaviruses is the most critical viral protein for cross-species transmission and infection. Here we determined the cryo-EM structures of the spikes from bat (RaTG13) and pangolin (PCoV_GX) coronaviruses, which are closely related to SARS-CoV-2. All three receptor-binding domains (RBDs) of these two spike trimers are in the "down" conformation, indicating they are more prone to adopt the receptor-binding inactive state. However, we found that the PCoV_GX, but not the RaTG13, spike is comparable to the SARS-CoV-2 spike in binding the human ACE2 receptor and supporting pseudovirus cell entry. We further identified critical residues in the RBD underlying different activities of the RaTG13 and PCoV_GX/SARS-CoV-2 spikes. These results collectively indicate that tight RBD-ACE2 binding and efficient RBD conformational sampling are required for the evolution of SARS-CoV-2 to gain highly efficient infection.


Asunto(s)
/virología , Quirópteros/virología , Coronavirus/química , Coronavirus/genética , /química , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Secuencia de Aminoácidos , Animales , /transmisión , Microscopía por Crioelectrón , Evolución Molecular , Interacciones Microbiota-Huesped , Humanos , Modelos Moleculares , Pandemias , Dominios Proteicos , Homología de Secuencia de Aminoácido , Especificidad de la Especie , Glicoproteína de la Espiga del Coronavirus/ultraestructura
3.
Medicina (Kaunas) ; 57(2)2021 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-33673004

RESUMEN

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a global pandemic and is posing a serious challenge to mankind. As per the current scenario, there is an urgent need for antiviral that could act as a protective and therapeutic against SARS-CoV-2. Previous studies have shown that SARS-CoV-2 is much similar to the SARS-CoV bat that occurred in 2002-03. Since it is a zoonotic virus, the exact source is still unknown, but it is believed bats may be the primary reservoir of SARS-CoV-2 through which it has been transferred to humans. In this review, we have tried to summarize some of the approaches that could be effective against SARS-CoV-2. Firstly, plants or plant-based products have been effective against different viral diseases, and secondly, plants or plant-based natural products have the minimum adverse effect. We have also highlighted a few vitamins and minerals that could be beneficial against SARS-CoV-2.


Asunto(s)
Antivirales/uso terapéutico , Productos Biológicos/uso terapéutico , Nutrientes/uso terapéutico , Virosis/tratamiento farmacológico , Animales , Quirópteros/virología , Humanos
4.
BMC Microbiol ; 21(1): 89, 2021 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-33757449

RESUMEN

BACKGROUND: When a virus that has grown in a nonhuman host starts an epidemic in the human population, human cells may not provide growth conditions ideal for the virus. Therefore, the invasion of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is usually prevalent in the bat population, into the human population is thought to have necessitated changes in the viral genome for efficient growth in the new environment. In the present study, to understand host-dependent changes in coronavirus genomes, we focused on the mono- and oligonucleotide compositions of SARS-CoV-2 genomes and investigated how these compositions changed time-dependently in the human cellular environment. We also compared the oligonucleotide compositions of SARS-CoV-2 and other coronaviruses prevalent in humans or bats to investigate the causes of changes in the host environment. RESULTS: Time-series analyses of changes in the nucleotide compositions of SARS-CoV-2 genomes revealed a group of mono- and oligonucleotides whose compositions changed in a common direction for all clades, even though viruses belonging to different clades should evolve independently. Interestingly, the compositions of these oligonucleotides changed towards those of coronaviruses that have been prevalent in humans for a long period and away from those of bat coronaviruses. CONCLUSIONS: Clade-independent, time-dependent changes are thought to have biological significance and should relate to viral adaptation to a new host environment, providing important clues for understanding viral host adaptation mechanisms.


Asunto(s)
Composición de Base , Evolución Molecular , Genoma Viral , /genética , Animales , Quirópteros/virología , Humanos , Oligonucleótidos
7.
Viruses ; 13(2)2021 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-33562073

RESUMEN

The contemporary surge in metagenomic sequencing has transformed knowledge of viral diversity in wildlife. However, evaluating which newly discovered viruses pose sufficient risk of infecting humans to merit detailed laboratory characterization and surveillance remains largely speculative. Machine learning algorithms have been developed to address this imbalance by ranking the relative likelihood of human infection based on viral genome sequences, but are not yet routinely applied to viruses at the time of their discovery. Here, we characterized viral genomes detected through metagenomic sequencing of feces and saliva from common vampire bats (Desmodus rotundus) and used these data as a case study in evaluating zoonotic potential using molecular sequencing data. Of 58 detected viral families, including 17 which infect mammals, the only known zoonosis detected was rabies virus; however, additional genomes were detected from the families Hepeviridae, Coronaviridae, Reoviridae, Astroviridae and Picornaviridae, all of which contain human-infecting species. In phylogenetic analyses, novel vampire bat viruses most frequently grouped with other bat viruses that are not currently known to infect humans. In agreement, machine learning models built from only phylogenetic information ranked all novel viruses similarly, yielding little insight into zoonotic potential. In contrast, genome composition-based machine learning models estimated different levels of zoonotic potential, even for closely related viruses, categorizing one out of four detected hepeviruses and two out of three picornaviruses as having high priority for further research. We highlight the value of evaluating zoonotic potential beyond ad hoc consideration of phylogeny and provide surveillance recommendations for novel viruses in a wildlife host which has frequent contact with humans and domestic animals.


Asunto(s)
Quirópteros/virología , Virus/aislamiento & purificación , Zoonosis/virología , Animales , Reservorios de Enfermedades/veterinaria , Reservorios de Enfermedades/virología , Heces/virología , Genoma Viral/genética , Humanos , Aprendizaje Automático , Metagenómica , Filogenia , Virus de la Rabia/clasificación , Virus de la Rabia/genética , Virus de la Rabia/aislamiento & purificación , Saliva/virología , Virus/clasificación , Virus/genética
8.
Viruses ; 13(2)2021 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-33572857

RESUMEN

Three major outbreaks of the coronavirus, a zoonotic virus known to cause respiratory disease, have been reported since 2002, including SARS-CoV, MERS-CoV and the most recent 2019-nCoV, or more recently known as SARS-CoV-2. Bats are known to be the primary animal reservoir for coronaviruses. However, in the past few decades, the virus has been able to mutate and adapt to infect humans, resulting in an animal-to-human species barrier jump. The emergence of a novel coronavirus poses a serious global public health threat and possibly carries the potential of causing a major pandemic outbreak in the naïve human population. The recent outbreak of COVID-19, the disease caused by SARS-CoV-2, in Wuhan, Hubei Province, China has infected over 36.5 million individuals and claimed over one million lives worldwide, as of 8 October 2020. The novel virus is rapidly spreading across China and has been transmitted to 213 other countries/territories across the globe. Researchers have reported that the virus is constantly evolving and spreading through asymptomatic carriers, further suggesting a high global health threat. To this end, current up-to-date information on the coronavirus evolution and SARS-CoV-2 modes of transmission, detection techniques and current control and prevention strategies are summarized in this review.


Asunto(s)
/prevención & control , /aislamiento & purificación , Animales , /terapia , China/epidemiología , Quirópteros/virología , Salud Global , Humanos , Pandemias , Salud Pública , /transmisión , /virología
9.
J Vet Sci ; 22(1): e12, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33522164

RESUMEN

BACKGROUND: Bats have been considered natural reservoirs for several pathogenic human coronaviruses (CoVs) in the last two decades. Recently, a bat CoV was detected in the Republic of Korea; its entire genome was sequenced and reported to be genetically similar to that of the severe acute respiratory syndrome CoV (SARS-CoV). OBJECTIVES: The objective of this study was to compare the genetic sequences of SARS-CoV, SARS-CoV-2, and the two Korean bat CoV strains 16BO133 and B15-21, to estimate the likelihood of an interaction between the Korean bat CoVs and the human angiotensin-converting enzyme 2 (ACE2) receptor. METHODS: The phylogenetic analysis was conducted with the maximum-likelihood (ML) method using MEGA 7 software. The Korean bat CoVs receptor binding domain (RBD) of the spike protein was analyzed by comparative homology modeling using the SWISS-MODEL server. The binding energies of the complexes were calculated using PRODIGY and MM/GBGA. RESULTS: Phylogenetic analyses of the entire RNA-dependent RNA polymerase, spike regions, and the complete genome revealed that the Korean CoVs, along with SARS-CoV and SARS-CoV-2, belong to the subgenus Sarbecovirus, within BetaCoVs. However, the two Korean CoVs were distinct from SARS-CoV-2. Specifically, the spike gene of the Korean CoVs, which is involved in host infection, differed from that of SARS-CoV-2, showing only 66.8%-67.0% nucleotide homology and presented deletions within the RBD, particularly within regions critical for cross-species transmission and that mediate interaction with ACE2. Binding free energy calculation revealed that the binding affinity of Korean bat CoV RBD to hACE2 was drastically lower than that of SARS-CoV and SARS-CoV-2. CONCLUSIONS: These results suggest that Korean bat CoVs are unlikely to bind to the human ACE2 receptor.


Asunto(s)
Quirópteros/virología , Coronavirus/genética , Virus del SRAS/genética , /genética , Animales , Genes Virales/genética , Genoma Viral/genética , Genómica , Humanos , Funciones de Verosimilitud , Filogenia , Receptor de Angiotensina Tipo 2/genética , Receptor de Angiotensina Tipo 2/metabolismo , República de Corea , Análisis de Secuencia de ADN , Homología de Secuencia , Glicoproteína de la Espiga del Coronavirus/genética , Acoplamiento Viral
10.
Nat Commun ; 12(1): 972, 2021 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-33563978

RESUMEN

Among the many questions unanswered for the COVID-19 pandemic are the origin of SARS-CoV-2 and the potential role of intermediate animal host(s) in the early animal-to-human transmission. The discovery of RaTG13 bat coronavirus in China suggested a high probability of a bat origin. Here we report molecular and serological evidence of SARS-CoV-2 related coronaviruses (SC2r-CoVs) actively circulating in bats in Southeast Asia. Whole genome sequences were obtained from five independent bats (Rhinolophus acuminatus) in a Thai cave yielding a single isolate (named RacCS203) which is most related to the RmYN02 isolate found in Rhinolophus malayanus in Yunnan, China. SARS-CoV-2 neutralizing antibodies were also detected in bats of the same colony and in a pangolin at a wildlife checkpoint in Southern Thailand. Antisera raised against the receptor binding domain (RBD) of RmYN02 was able to cross-neutralize SARS-CoV-2 despite the fact that the RBD of RacCS203 or RmYN02 failed to bind ACE2. Although the origin of the virus remains unresolved, our study extended the geographic distribution of genetically diverse SC2r-CoVs from Japan and China to Thailand over a 4800-km range. Cross-border surveillance is urgently needed to find the immediate progenitor virus of SARS-CoV-2.


Asunto(s)
Quirópteros/virología , /fisiología , Secuencia de Aminoácidos , Animales , Anticuerpos Neutralizantes/sangre , Asia Sudoriental , Quirópteros/sangre , Geografía , Pruebas de Neutralización , Filogenia , Dominios Proteicos , Receptores de Superficie Celular/química , Receptores de Superficie Celular/metabolismo
11.
Viruses ; 13(2)2021 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-33525437

RESUMEN

The establishment of selective colonies of potential vertebrate hosts for viruses would provide experimental models for the understanding of pathogen-host interactions. This paper briefly surveys the reasons to conduct such studies and how the results might provide information that could be applied to disease prevention activities.


Asunto(s)
Reservorios de Enfermedades/virología , Interacciones Huésped-Patógeno , Animales , /transmisión , Quirópteros/virología , Coronavirus/clasificación , Coronavirus/genética , Coronavirus/patogenicidad , Especificidad del Huésped , Humanos , /genética , Zoonosis/prevención & control , Zoonosis/virología
12.
Pathog Dis ; 79(1)2021 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-33537740

RESUMEN

A vast proportion of coronavirus disease 2019 (COVID-19) individuals remain asymptomatic and can shed severe acute respiratory syndrome (SARS-CoV) type 2 virus to transmit the infection, which also explains the exponential increase in the number of COVID-19 cases globally. Furthermore, the rate of recovery from clinical COVID-19 in certain pockets of the globe is surprisingly high. Based on published reports and available literature, here, we speculated a few immunovirological mechanisms as to why a vast majority of individuals remain asymptomatic similar to exotic animal (bats and pangolins) reservoirs that remain refractile to disease development despite carrying a huge load of diverse insidious viral species, and whether such evolutionary advantage would unveil therapeutic strategies against COVID-19 infection in humans. Understanding the unique mechanisms that exotic animal species employ to achieve viral control, as well as inflammatory regulation, appears to hold key clues to the development of therapeutic versatility against COVID-19.


Asunto(s)
Animales Exóticos/virología , /virología , Reservorios de Enfermedades/virología , Inmunidad Innata/inmunología , /inmunología , Animales , Infecciones Asintomáticas , Quirópteros/virología , Humanos , /virología
13.
Comput Biol Med ; 131: 104247, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33611129

RESUMEN

A non-standard bioinformatics method, 4D-Dynamic Representation of DNA/RNA Sequences, aiming at an analysis of the information available in nucleotide databases, has been formulated. The sequences are represented by sets of "material points" in a 4D space - 4D-dynamic graphs. The graphs representing the sequences are treated as "rigid bodies" and characterized by values analogous to the ones used in the classical dynamics. As the graphical representations of the sequences, the projections of the graphs into 2D and 3D spaces are used. The method has been applied to an analysis of the complete genome sequences of the 2019 novel coronavirus. As a result, 2D and 3D classification maps are obtained. The coordinate axes in the maps correspond to the values derived from the exact formulas characterizing the graphs: the coordinates of the centers of mass and the 4D moments of inertia. The points in the maps represent sequences and their coordinates are used as the classifiers. The main result of this work has been derived from the 3D classification maps. The distribution of clusters of points which emerged in these maps, supports the hypothesis that SARS-CoV-2 may have originated in bat and in pangolin. Pilot calculations for Zika virus sequence data prove that the proposed approach is also applicable to a description of time evolution of genome sequences of viruses.


Asunto(s)
Algoritmos , Secuencia de Bases , Biología Computacional , Genoma Viral , /genética , Animales , Quirópteros/virología , Humanos , Filogenia , Virus Zika/genética , Infección por el Virus Zika/genética
14.
Nature ; 591(7850): 451-457, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33561864

RESUMEN

All coronaviruses known to have recently emerged as human pathogens probably originated in bats1. Here we use a single experimental platform based on immunodeficient mice implanted with human lung tissue (hereafter, human lung-only mice (LoM)) to demonstrate the efficient in vivo replication of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as two endogenous SARS-like bat coronaviruses that show potential for emergence as human pathogens. Virus replication in this model occurs in bona fide human lung tissue and does not require any type of adaptation of the virus or the host. Our results indicate that bats contain endogenous coronaviruses that are capable of direct transmission to humans. Our detailed analysis of in vivo infection with SARS-CoV-2 in human lung tissue from LoM showed a predominant infection of human lung epithelial cells, including type-2 pneumocytes that are present in alveoli and ciliated airway cells. Acute infection with SARS-CoV-2 was highly cytopathic and induced a robust and sustained type-I interferon and inflammatory cytokine and chemokine response. Finally, we evaluated a therapeutic and pre-exposure prophylaxis strategy for SARS-CoV-2 infection. Our results show that therapeutic and prophylactic administration of EIDD-2801-an oral broad-spectrum antiviral agent that is currently in phase II/III clinical trials-markedly inhibited SARS-CoV-2 replication in vivo, and thus has considerable potential for the prevention and treatment of COVID-19.


Asunto(s)
/tratamiento farmacológico , Citidina/análogos & derivados , Hidroxilaminas/administración & dosificación , Hidroxilaminas/uso terapéutico , Administración Oral , Células Epiteliales Alveolares/inmunología , Células Epiteliales Alveolares/patología , Células Epiteliales Alveolares/virología , Animales , Quimioprevención , Quirópteros/virología , Ensayos Clínicos Fase II como Asunto , Ensayos Clínicos Fase III como Asunto , Citidina/administración & dosificación , Citidina/uso terapéutico , Citocinas/inmunología , Células Epiteliales/virología , Femenino , Xenoinjertos , Humanos , Inmunidad Innata , Interferón Tipo I/inmunología , Pulmón/inmunología , Pulmón/patología , Pulmón/virología , Trasplante de Pulmón , Masculino , Ratones , Profilaxis Posexposición , Profilaxis Pre-Exposición , /patogenicidad , Replicación Viral
15.
BMC Infect Dis ; 21(1): 162, 2021 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-33563231

RESUMEN

BACKGROUND: In June 2019, Nipah virus (NiV) infection was detected in a 21-year-old male (index case) of Ernakulum, Kerala, India. This study was undertaken to determine if NiV was in circulation in Pteropus species (spp) in those areas where the index case had visit history in 1 month. METHODS: Specialized techniques were used to trap the Pteropus medius bats (random sampling) in the vicinity of the index case area. Throat and rectal swabs samples of 141 bats along with visceral organs of 92 bats were collected to detect the presence of NiV by real-time reverse transcriptase-polymerase chain reaction (qRTPCR). Serum samples of 52 bats were tested for anti-NiV Immunoglobulin (Ig) G antibodies by Enzyme-Linked Immunosorbent Assay (ELISA). The complete genome of NiV was sequenced by next-generation sequencing (NGS) from the tissues and swab samples of bats. RESULTS: One rectal swab sample and three bats visceral organs were found positive for the NiV. Interestingly, 20.68% (12/58) of Pteropus were positive for anti-NiV IgG antibodies. NiV sequences of 18,172; 17,200 and 15,100 nucleotide bps could be retrieved from three Pteropus bats. CONCLUSION: A distinct cluster of NiV sequences, with significant net-evolutionary nucleotide divergence, was obtained, suggesting the circulation of new genotype (I-India) in South India. NiV Positivity in Pteropus spp. of bats revealed that NiV is circulating in many districts of Kerala state, and active surveillance of NiV should be immediately set up to know the hotspot area for NiV infection.


Asunto(s)
Quirópteros/virología , Infecciones por Henipavirus/diagnóstico , Virus Nipah/genética , Animales , Anticuerpos Antivirales/sangre , Brotes de Enfermedades , Infecciones por Henipavirus/epidemiología , Infecciones por Henipavirus/veterinaria , Infecciones por Henipavirus/virología , Secuenciación de Nucleótidos de Alto Rendimiento , Inmunoglobulina G/sangre , India/epidemiología , Virus Nipah/clasificación , Virus Nipah/inmunología , Filogenia , ARN Viral/química , ARN Viral/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Recto/virología
16.
J Wildl Dis ; 57(1): 238-241, 2021 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-33635981

RESUMEN

The global SARS-CoV-2 pandemic and the role of bats in zoonotic spillover have renewed interest in the flight-as-fever hypothesis, which posits that high body temperatures experienced by bats during flight contribute to their high viral tolerance. We argue that flight-as-fever is unlikely to explain why bats harbor more viruses than other mammals on the basis of two lines of reasoning. First, flight temperatures reported in the literature overestimate true flight temperatures because of methodologic limitations. Second, body temperatures in bats are only high relative to humans, and not relative to many other mammals. We provide examples of mammals from diverse habitats to show that temperatures in excess of 40 C during activity are quite common in species with lower viral diversity than bats. We caution scientists against stating the flight-as-fever hypothesis as unquestioned truth, as has repeatedly occurred in the popular media in the wake of the SARS-CoV-2 pandemic.


Asunto(s)
Temperatura Corporal/fisiología , Quirópteros/fisiología , Quirópteros/virología , /fisiología , Animales , Portador Sano/veterinaria , Portador Sano/virología , Reservorios de Enfermedades/virología , Vuelo Animal/fisiología , Zoonosis
18.
Hist Philos Life Sci ; 43(1): 7, 2021 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-33439354

RESUMEN

What should the best practices be for modeling zoonotic disease risks, e.g. to anticipate the next pandemic, when background assumptions are unsettled or evolving rapidly? This challenge runs deeper than one might expect, all the way into how we model the robustness of contemporary phylogenetic inference and taxonomic classifications. Different and legitimate taxonomic assumptions can destabilize the putative objectivity of zoonotic risk assessments, thus potentially supporting inconsistent and overconfident policy decisions.


Asunto(s)
Quirópteros , Pandemias , Medición de Riesgo/métodos , Zoonosis , Animales , Quirópteros/virología , Humanos , Modelos Teóricos , Pandemias/clasificación , Filogenia , Zoonosis/epidemiología , Zoonosis/transmisión , Zoonosis/virología
19.
Viruses ; 13(2)2021 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-33498685

RESUMEN

Nipah virus is a bat-borne paramyxovirus that produces yearly outbreaks of fatal encephalitis in Bangladesh. Understanding the ecological conditions that lead to spillover from bats to humans can assist in designing effective interventions. To investigate the current and historical processes that drive Nipah spillover in Bangladesh, we analyzed the relationship among spillover events and climatic conditions, the spatial distribution and size of Pteropus medius roosts, and patterns of land-use change in Bangladesh over the last 300 years. We found that 53% of annual variation in winter spillovers is explained by winter temperature, which may affect bat behavior, physiology, and human risk behaviors. We infer from changes in forest cover that a progressive shift in bat roosting behavior occurred over hundreds of years, producing the current system where a majority of P. medius populations are small (median of 150 bats), occupy roost sites for 10 years or more, live in areas of high human population density, and opportunistically feed on cultivated food resources-conditions that promote viral spillover. Without interventions, continuing anthropogenic pressure on bat populations similar to what has occurred in Bangladesh could result in more regular spillovers of other bat viruses, including Hendra and Ebola viruses.


Asunto(s)
Quirópteros/virología , Conducta Alimentaria , Infecciones por Henipavirus/epidemiología , Infecciones por Henipavirus/veterinaria , Virus Nipah/genética , Animales , Bangladesh/epidemiología , Quirópteros/fisiología , Brotes de Enfermedades , Bosques , Humanos , Modelos Lineales , Estaciones del Año , Zoonosis/epidemiología , Zoonosis/virología
20.
Future Microbiol ; 16: 107-118, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33459559

RESUMEN

Viruses have caused the death of millions of people worldwide. Specifically, human viruses are grouped into 21 families, including the family of coronaviruses (CoVs). In December 2019, in Wuhan, China, a new human CoV was identified, SARS-CoV-2. The first step of the infection mechanism of the SARS-CoV-2 in the human host is adhesion, which occurs through the S glycoprotein that is found in diverse human organs. Another way through which SARS-CoV-2 could possibly attach to the host's cells is by means of the histo-blood group antigens. In this work, we have reviewed the mechanisms by which some viruses bind to the histo-blood group antigens, which could be related to the susceptibility of the individual and are dependent on the histo-blood group.


Asunto(s)
Antígenos de Grupos Sanguíneos/metabolismo , Glicoproteína de la Espiga del Coronavirus/metabolismo , Acoplamiento Viral , Animales , Quirópteros/virología , Susceptibilidad a Enfermedades/sangre , Genoma Viral/genética , Glicoproteínas/metabolismo , Humanos , /genética
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