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1.
Cell ; 184(24): 5950-5969.e22, 2021 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-34741801

RESUMEN

The biogenesis of mammalian autophagosomes remains to be fully defined. Here, we used cellular and in vitro membrane fusion analyses to show that autophagosomes are formed from a hitherto unappreciated hybrid membrane compartment. The autophagic precursors emerge through fusion of FIP200 vesicles, derived from the cis-Golgi, with endosomally derived ATG16L1 membranes to generate a hybrid pre-autophagosomal structure, HyPAS. A previously unrecognized apparatus defined here controls HyPAS biogenesis and mammalian autophagosomal precursor membranes. HyPAS can be modulated by pharmacological agents whereas its formation is inhibited upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or by expression of SARS-CoV-2 nsp6. These findings reveal the origin of mammalian autophagosomal membranes, which emerge via convergence of secretory and endosomal pathways, and show that this process is targeted by microbial factors such as coronaviral membrane-modulating proteins.


Asunto(s)
Autofagosomas/virología , COVID-19/virología , Autofagia , COVID-19/metabolismo , Sistemas CRISPR-Cas , Línea Celular Tumoral , Retículo Endoplásmico/metabolismo , Endosomas/fisiología , Endosomas/virología , Aparato de Golgi/fisiología , Células HEK293 , Células HeLa , Humanos , Fusión de Membrana , Microscopía Confocal , Fagosomas/metabolismo , Fagosomas/virología , Proteínas Qa-SNARE/biosíntesis , Receptores sigma/biosíntesis , SARS-CoV-2 , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/biosíntesis , Sinaptotagminas/biosíntesis , Receptor Sigma-1
2.
Emerg Infect Dis ; 30(4): 817-821, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38526320

RESUMEN

Orthohantaviruses cause hantavirus cardiopulmonary syndrome; most cases occur in the southwest region of the United States. We discuss a clinical case of orthohantavirus infection in a 65-year-old woman in Michigan and the phylogeographic link of partial viral fragments from the patient and rodents captured near the presumed site of infection.


Asunto(s)
Infecciones por Hantavirus , Orthohantavirus , Femenino , Humanos , Anciano , Michigan/epidemiología , Filogeografía , Síndrome
3.
J Gen Virol ; 105(4)2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38587456

RESUMEN

Hantaviridae is a family for negative-sense RNA viruses with genomes of about 10.5-14.6 kb. These viruses are maintained in and/or transmitted by fish, reptiles, and mammals. Several orthohantaviruses can infect humans, causing mild, severe, and sometimes-fatal diseases. Hantavirids produce enveloped virions containing three single-stranded RNA segments with open reading frames that encode a nucleoprotein (N), a glycoprotein precursor (GPC), and a large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Hantaviridae, which is available at ictv.global/report/hantaviridae.


Asunto(s)
Virus ARN , Animales , Humanos , Virus ARN de Sentido Negativo , Virión/genética , Nucleoproteínas , Sistemas de Lectura Abierta , Mamíferos
4.
J Gen Virol ; 104(8)2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37622664

RESUMEN

In April 2023, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by one new family, 14 new genera, and 140 new species. Two genera and 538 species were renamed. One species was moved, and four were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.


Asunto(s)
Virus ARN de Sentido Negativo , Virus ARN , Virus ARN/genética , ARN Polimerasa Dependiente del ARN/genética
5.
J Virol ; 95(23): e0153421, 2021 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-34549977

RESUMEN

Sin Nombre orthohantavirus (SNV), a negative-sense, single-stranded RNA virus that is carried and transmitted by the North American deer mouse Peromyscus maniculatus, can cause infection in humans through inhalation of aerosolized excreta from infected rodents. This infection can lead to hantavirus cardiopulmonary syndrome (HCPS), which has an ∼36% case-fatality rate. We used reverse transcriptase quantitative PCR (RT-qPCR) to confirm SNV infection in a patient and identified SNV in lung tissues in wild-caught rodents from potential sites of exposure. Using viral whole-genome sequencing (WGS), we identified the likely site of transmission and discovered SNV in multiple rodent species not previously known to carry the virus. Here, we report, for the first time, the use of SNV WGS to pinpoint a likely site of human infection and identify SNV simultaneously in multiple rodent species in an area of known host-to-human transmission. These results will impact epidemiology and infection control for hantaviruses by tracing zoonotic transmission and investigating possible novel host reservoirs. IMPORTANCE Orthohantaviruses cause severe disease in humans and can be lethal in up to 40% of cases. Sin Nombre orthohantavirus (SNV) is the main cause of hantavirus disease in North America. In this study, we sequenced SNV from an infected patient and wild-caught rodents to trace the location of infection. We also discovered SNV in rodent species not previously known to carry SNV. These studies demonstrate for the first time the use of virus sequencing to trace the transmission of SNV and describe infection in novel rodent species.


Asunto(s)
Reservorios de Enfermedades/virología , Síndrome Pulmonar por Hantavirus/transmisión , Síndrome Pulmonar por Hantavirus/veterinaria , Síndrome Pulmonar por Hantavirus/virología , Enfermedades de los Roedores/transmisión , Enfermedades de los Roedores/virología , Roedores/virología , Virus Sin Nombre , Animales , Anticuerpos Antivirales , Secuencia de Bases , Femenino , Orthohantavirus/genética , Infecciones por Hantavirus/genética , Infecciones por Hantavirus/transmisión , Infecciones por Hantavirus/veterinaria , Síndrome Pulmonar por Hantavirus/epidemiología , Humanos , Pulmón , Masculino , Ratones , América del Norte , Peromyscus/virología , Prevalencia , ARN Viral/genética , Enfermedades de los Roedores/epidemiología , Virus Sin Nombre/genética , Población Blanca , Secuenciación Completa del Genoma
6.
Arch Virol ; 167(12): 2857-2906, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36437428

RESUMEN

In March 2022, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by two new families (bunyaviral Discoviridae and Tulasviridae), 41 new genera, and 98 new species. Three hundred forty-nine species were renamed and/or moved. The accidentally misspelled names of seven species were corrected. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.


Asunto(s)
Mononegavirales , Virus , Humanos , Mononegavirales/genética , Filogenia
7.
Glycobiology ; 31(4): 378-384, 2021 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-32985653

RESUMEN

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an unprecedented challenge for health care and the global economy. Repurposing drugs that have shown promise in inhibiting other viral infections could allow for more rapid dispensation of urgently needed therapeutics. The Spike protein of SARS-CoV-2 is extensively glycosylated with 22 occupied N glycan sites and is required for viral entry. In other glycosylated viral proteins, glycosylation is required for interaction with calnexin and chaperone-mediated folding in the endoplasmic reticulum, and prevention of this interaction leads to unfolded viral proteins and thus inhibits viral replication. As such, we investigated two iminosugars, celgosivir, a prodrug of castanospermine, and UV-4, or N-(9-methoxynonyl)-1-deoxynojirimycin, a deoxynojirimycin derivative. Iminosugars are known inhibitors of the α-glucosidase I and II enzymes and were effective at inhibiting authentic SARS-CoV-2 viral replication in a cell culture system. Celgosivir prevented SARS-CoV-2-induced cell death and reduced viral replication and Spike protein levels in a dose-dependent manner in culture with Vero E6 cells. Castanospermine, the active form of celgosivir, was also able to inhibit SARS-CoV-2, confirming the canonical castanospermine mechanism of action of celgosivir. The monocyclic UV-4 also prevented SARS-CoV-2-induced death and reduced viral replication after 24 h of treatment, although the reduction in viral copies was lost after 48 h. Our findings suggest that iminosugars should be urgently investigated as potential SARS-CoV-2 inhibitors.


Asunto(s)
1-Desoxinojirimicina/análogos & derivados , Tratamiento Farmacológico de COVID-19 , Indolizinas/farmacología , SARS-CoV-2/efectos de los fármacos , Replicación Viral/efectos de los fármacos , 1-Desoxinojirimicina/farmacología , Animales , COVID-19/virología , Chlorocebus aethiops , Inhibidores de Glicósido Hidrolasas/farmacología , Humanos , Células Vero
8.
Immunity ; 37(2): 223-34, 2012 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-22921120

RESUMEN

Autophagy is a fundamental biological process of the eukaryotic cell contributing to diverse cellular and physiological functions including cell-autonomous defense against intracellular pathogens. Here, we screened the Rab family of membrane trafficking regulators for effects on autophagic elimination of Mycobacterium tuberculosis var. bovis BCG and found that Rab8b and its downstream interacting partner, innate immunity regulator TBK-1, are required for autophagic elimination of mycobacteria in macrophages. TBK-1 was necessary for autophagic maturation. TBK-1 coordinated assembly and function of the autophagic machinery and phosphorylated the autophagic adaptor p62 (sequestosome 1) on Ser-403, a residue essential for its role in autophagic clearance. A key proinflammatory cytokine, IL-1ß, induced autophagy leading to autophagic killing of mycobacteria in macrophages, and this IL-1ß activity was dependent on TBK-1. Thus, TBK-1 is a key regulator of immunological autophagy and is responsible for the maturation of autophagosomes into lytic bactericidal organelles.


Asunto(s)
Autofagia/inmunología , Macrófagos/inmunología , Proteínas Serina-Treonina Quinasas/inmunología , Proteínas de Unión al GTP rab/inmunología , Proteínas Adaptadoras Transductoras de Señales/inmunología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Proteína 7 Relacionada con la Autofagia , Proteínas Fluorescentes Verdes , Células HeLa , Proteínas de Choque Térmico/inmunología , Proteínas de Choque Térmico/metabolismo , Humanos , Interleucina-1beta/inmunología , Interleucina-1beta/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Microscopía Confocal , Proteínas Asociadas a Microtúbulos/antagonistas & inhibidores , Proteínas Asociadas a Microtúbulos/genética , Mycobacterium bovis/inmunología , Fagosomas/efectos de los fármacos , Fagosomas/inmunología , Fagosomas/metabolismo , Fosforilación , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/metabolismo , ARN Interferente Pequeño , Proteína Sequestosoma-1 , Serina/inmunología , Serina/metabolismo , Tuberculosis/inmunología , Proteínas de Unión al GTP rab/genética
9.
Arch Virol ; 166(12): 3513-3566, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34463877

RESUMEN

In March 2021, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by four families (Aliusviridae, Crepuscuviridae, Myriaviridae, and Natareviridae), three subfamilies (Alpharhabdovirinae, Betarhabdovirinae, and Gammarhabdovirinae), 42 genera, and 200 species. Thirty-nine species were renamed and/or moved and seven species were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.


Asunto(s)
Mononegavirales , Virus , Humanos
10.
J Infect Dis ; 222(10): 1620-1628, 2020 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-32779705

RESUMEN

BACKGROUND: Convalescent plasma (CP) is a potentially important therapy for coronavirus disease 2019 (COVID-19). However, knowledge regarding neutralizing antibody (NAb) titers in donor plasma and their impact in patients with acute COVID-19 remains largely undetermined. We measured NAb titers in CP and in patients with acute COVID-19 before and after transfusion through the traditional Food and Drug Administration investigational new drug pathway. METHODS: We performed a single-arm interventional trial measuring NAb and total antibody titers before and after CP transfusion over a 14-day period in hospitalized patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection. RESULTS: NAb titers in the donor CP units were low (<1:40 to 1:160) and had no effect on recipient neutralizing activity 1 day after transfusion. NAb titers were detected in 6 of 12 patients on enrollment and in 11 of 12 at ≥2 time points. Average titers peaked on day 7 and declined toward day 14 (P = .004). Nab titers and immunoglobulin G levels were correlated in donor plasma units (ρ = 0.938; P < .001) and in the cumulative patient measures (ρ = 0.781; P < .001). CONCLUSIONS: CP infusion did not alter recipient NAb titers. Prescreening of CP may be necessary for selecting donors with high titers of neutralizing activity for infusion into patients with COVID-19. CLINICAL TRIALS REGISTRATION: NCT04434131.


Asunto(s)
Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Betacoronavirus/inmunología , Donantes de Sangre , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/terapia , Neumonía Viral/epidemiología , Neumonía Viral/terapia , Adulto , Anciano , Anciano de 80 o más Años , Betacoronavirus/genética , COVID-19 , Estudios de Cohortes , Infecciones por Coronavirus/virología , Femenino , Humanos , Inmunización Pasiva , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , New Mexico/epidemiología , Pandemias , Neumonía Viral/virología , ARN Viral/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/inmunología , Resultado del Tratamiento , Sueroterapia para COVID-19
11.
Arch Virol ; 165(12): 3023-3072, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32888050

RESUMEN

In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.


Asunto(s)
Mononegavirales/clasificación , Terminología como Asunto
14.
Virol J ; 12: 152, 2015 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-26420265

RESUMEN

BACKGROUND: Eastern equine encephalitis virus (EEEV), an arbovirus, is an important human and veterinary pathogen belonging to one of seven antigenic complexes in the genus Alphavirus, family Togaviridae. EEEV is considered the most deadly of the mosquito-borne alphaviruses due to the high case fatality rate associated with clinical infections, reaching up to 75 % in humans and 90 % in horses. In patients that survive acute infection, neurologic sequelae are often devastating. Although natural infections are acquired by mosquito bite, EEEV is also highly infectious by aerosol. This fact, along with the relative ease of production and stability of this virus, has led it to being identified as a potential agent of bioterrorism. METHODS: To characterize the clinical course and outcome of EEEV strain FL93-939 infection, we compared clinical parameters, cytokine expression, viremia, and viral titers in numerous tissues of mice exposed by various routes. Twelve-week-old female BALB/c mice were infected by the intranasal, aerosol, or subcutaneous route. Mice were monitored for clinical signs of disease and euthanized at specified time points (6 hpi through 8 dpi). Blood and tissues were harvested for cytokine analysis and/or viral titer determination. RESULTS: Although all groups of animals exhibited similar clinical signs after inoculation, the onset and severity differed. The majority of those animals exposed by the aerosol route developed severe clinical signs by 4 dpi. Significant differences were also observed in the viral titers of target tissues, with virus being detected in the brain at 6 hpi in the aerosol study. CONCLUSION: The clinical course and outcome of EEEV infection in mice is dependent on route of exposure. Aerosol exposure to EEEV results in acute onset of clinical signs, rapid neuroinvasion, and 100 % mortality.


Asunto(s)
Infecciones por Alphavirus/patología , Modelos Animales de Enfermedad , Virus de la Encefalitis Equina del Este/crecimiento & desarrollo , Virus de la Encefalitis Equina del Este/patogenicidad , Administración por Inhalación , Administración Intranasal , Infecciones por Alphavirus/virología , Estructuras Animales/patología , Estructuras Animales/virología , Animales , Líquidos Corporales/virología , Citocinas/análisis , Femenino , Inyecciones Subcutáneas , Ratones Endogámicos BALB C , Análisis de Supervivencia , Carga Viral
15.
Arch Virol ; 159(5): 1229-37, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24190508

RESUMEN

Specific alterations (mutations, deletions, insertions) of virus genomes are crucial for the functional characterization of their regulatory elements and their expression products, as well as a prerequisite for the creation of attenuated viruses that could serve as vaccine candidates. Virus genome tailoring can be performed either by using traditionally cloned genomes as starting materials, followed by site-directed mutagenesis, or by de novo synthesis of modified virus genomes or parts thereof. A systematic nomenclature for such recombinant viruses is necessary to set them apart from wild-type and laboratory-adapted viruses, and to improve communication and collaborations among researchers who may want to use recombinant viruses or create novel viruses based on them. A large group of filovirus experts has recently proposed nomenclatures for natural and laboratory animal-adapted filoviruses that aim to simplify the retrieval of sequence data from electronic databases. Here, this work is extended to include nomenclature for filoviruses obtained in the laboratory via reverse genetics systems. The previously developed template for natural filovirus genetic variant naming, (/)///-, is retained, but we propose to adapt the type of information added to each field for cDNA clone-derived filoviruses. For instance, the full-length designation of an Ebola virus Kikwit variant rescued from a plasmid developed at the US Centers for Disease Control and Prevention could be akin to "Ebola virus H.sapiens-rec/COD/1995/Kikwit-abc1" (with the suffix "rec" identifying the recombinant nature of the virus and "abc1" being a placeholder for any meaningful isolate designator). Such a full-length designation should be used in databases and the methods section of publications. Shortened designations (such as "EBOV H.sap/COD/95/Kik-abc1") and abbreviations (such as "EBOV/Kik-abc1") could be used in the remainder of the text, depending on how critical it is to convey information contained in the full-length name. "EBOV" would suffice if only one EBOV strain/variant/isolate is addressed.


Asunto(s)
Filoviridae/clasificación , Filoviridae/genética , Virus Reordenados/clasificación , Virus Reordenados/genética , Genoma Viral
16.
PLoS One ; 19(1): e0296718, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38236803

RESUMEN

Orthohantaviruses are diverse zoonotic RNA viruses. Small mammals, such as mice and rats are common chronic, asymptomatic hosts that transmit the virus through their feces and urine. In North America, hantavirus infection primarily causes hantavirus cardiopulmonary syndrome (HCPS), which has a mortality rate of nearly 36%. In the United States of America, New Mexico (NM) is leading the nation in the number of HCPS-reported cases (N = 129). However, no reported cases of HCPS have occurred within eastern NM. In this study, we assessed the prevalence of Sin Nombre virus (SNV) in rodent assemblages across eastern NM, using RT-qPCR. We screened for potential rodent hosts in the region, as well as identified areas that may pose significant infection risk to humans. We captured and collected blood and lung tissues from 738 rodents belonging to 23 species. 167 individuals from 16 different species were positive for SNV RNA by RT-qPCR, including 6 species unreported in the literature: Onychomys leucogaster (Northern grasshopper mouse), Dipodomys merriami (Merriam's kangaroo rat), Dipodomys ordii (Ord's kangaroo rat), Dipodomys spectabilis (Banner-tailed kangaroo rat), Perognathus flavus (Silky pocket mouse), and Chaetodipus hispidus (Hispid pocket mouse). The infection rates did not differ between sexes or rodent families (i.e., Cricetidae vs. Heteromyidae). Generalized linear model showed that disturbed habitat types positively influenced the prevalence of SNV at sites of survey. Overall, the results of this study indicate that many rodent species in east New Mexico have the potential to maintain SNV in the environment, but further research is needed to assess species specific infectivity mechanisms and potential risk to humans.


Asunto(s)
Infecciones por Hantavirus , Síndrome Pulmonar por Hantavirus , Orthohantavirus , Virus Sin Nombre , Humanos , Animales , Ratones , Roedores , Dipodomys , Virus Sin Nombre/genética , New Mexico/epidemiología , Prevalencia , Infecciones por Hantavirus/epidemiología , Infecciones por Hantavirus/veterinaria , Orthohantavirus/genética , Arvicolinae , Síndrome Pulmonar por Hantavirus/epidemiología , Síndrome Pulmonar por Hantavirus/veterinaria
17.
PLoS Negl Trop Dis ; 18(1): e0011672, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38215158

RESUMEN

BACKGROUND: Hantaviruses are negative-stranded RNA viruses that can sometimes cause severe disease in humans; however, they are maintained in mammalian host populations without causing harm. In Panama, sigmodontine rodents serve as hosts to transmissible hantaviruses. Due to natural and anthropogenic forces, these rodent populations are having increased contact with humans. METHODS: We extracted RNA and performed Illumina deep metatranscriptomic sequencing on Orthohantavirus seropositive museum tissues from rodents. We acquired sequence reads mapping to Choclo virus (CHOV, Orthohantavirus chocloense) from heart and kidney tissue of a two-decade old frozen museum sample from a Costa Rican pygmy rice rat (Oligoryzomys costaricensis) collected in Panama. Reads mapped to the CHOV reference were assembled and then validated by visualization of the mapped reads against the assembly. RESULTS: We recovered a 91% complete consensus sequence from a reference-guided assembly to CHOV with an average of 16X coverage. The S and M segments used in our phylogenetic analyses were nearly complete (98% and 99%, respectively). There were 1,199 ambiguous base calls of which 93% were present in the L segment. Our assembled genome varied 1.1% from the CHOV reference sequence resulting in eight nonsynonymous mutations. Further analysis of all publicly available partial S segment sequences support a clear relationship between CHOV clinical cases and O. costaricensis acquired strains. CONCLUSIONS: Viruses occurring at extremely low abundances can be recovered from deep metatranscriptomics of archival tissues housed in research natural history museum biorepositories. Our efforts resulted in the second CHOV genome publicly available. This genomic data is important for future surveillance and diagnostic tools as well as understanding the evolution and pathogenicity of CHOV.


Asunto(s)
Orthohantavirus , Sigmodontinae , Animales , Ratas , Humanos , Filogenia , Roedores , Bancos de Muestras Biológicas
18.
Antiviral Res ; 225: 105851, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38458540

RESUMEN

Currently, there are two approved vaccine regimens designed to prevent Ebola virus (EBOV) disease (EVD). Both are virus-vectored, and concerns about cold-chain storage and pre-existing immunity to the vectors warrant investigating additional vaccine strategies. Here, we have explored the utility of adjuvanted recombinant glycoproteins (GPs) from ebolaviruses Zaire (EBOV), Sudan (SUDV), and Bundibugyo (BDBV) for inducing antibody (Ab) and T cell cross-reactivity. Glycoproteins expressed in insect cells were administered to C57BL/6 mice as free protein or bound to the surface of liposomes, and formulated with toll-like receptor agonists CpG and MPLA (agonists for TLR 9 and 4, respectively), with or without the emulsions AddaVax or TiterMax. The magnitude of Ab cross-reactivity in binding and neutralization assays, and T cell cross-reactivity in antigen recall assays, correlated with phylogenetic relatedness. While most adjuvants screened induced IgG responses, a combination of CpG, MPLA and AddaVax emulsion ("IVAX-1") was the most potent and polarized in an IgG2c (Th1) direction. Breadth was also achieved by combining GPs into a trivalent (Tri-GP) cocktail with IVAX-1, which did not compromise antibody responses to individual components in binding and neutralizing assays. Th1 signature cytokines in T cell recall assays were undetectable after Tri-GP/IVAX-1 administration, despite a robust IgG2c response, although administration of Tri-GP on lipid nanoparticles in IVAX-1 elevated Th1 cytokines to detectable levels. Overall, the data indicate an adjuvanted trivalent recombinant GP approach may represent a path toward a broadly reactive, deployable vaccine against EVD.


Asunto(s)
Vacunas contra el Virus del Ébola , Ebolavirus , Fiebre Hemorrágica Ebola , Polisorbatos , Escualeno , Animales , Ratones , Anticuerpos Antivirales , Sudán , Filogenia , Anticuerpos Neutralizantes , Ratones Endogámicos C57BL , Glicoproteínas , Adyuvantes Inmunológicos , Linfocitos T , Citocinas
19.
Antiviral Res ; 210: 105493, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36567023

RESUMEN

Ebola virus (EBOV) is a member of the filoviridae family, which are comprised of negative sense, enveloped RNA hemorrhagic fever viruses that can cause severe disease and high lethality rates. These viruses require BSL-4 containment laboratories for study. Early studies of EBOV pathogenesis relied heavily on the use of nonhuman primates, which are expensive and cumbersome to handle in large numbers. Guinea pig models were also developed, but even to this day limited reagents are available in this model. In 1998, Mike Bray and colleagues developed a mouse-adapted EBOV (maEBOV) that caused lethality in adult immunocompetent mice. This model had significant advantages, including being inexpensive, allowing for higher animal numbers for statistical analysis, availability of reagents for studying pathogenesis, and availability of a vast array of genetically modified strains. The model has been used to test vaccines, therapeutic drugs, EBOV mutants, and pathogenesis, and its importance is demonstrated by the hundreds of citations referencing the original publication. This review will cover the history of the maEBOV model and its use in filovirus research.


Asunto(s)
Ebolavirus , Infecciones por Filoviridae , Fiebre Hemorrágica Ebola , Animales , Ratones , Cobayas , Ebolavirus/genética , Modelos Animales de Enfermedad
20.
Viruses ; 15(2)2023 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-36851776

RESUMEN

Alphaviruses are important human and animal pathogens that can cause a range of debilitating symptoms and are found worldwide. These include arthralgic diseases caused by Old-World viruses and encephalitis induced by infection with New-World alphaviruses. Non-coding RNAs do not encode for proteins, but can modulate cellular response pathways in a myriad of ways. There are several classes of non-coding RNAs, some more well-studied than others. Much research has focused on the mRNA response to infection against alphaviruses, but analysis of non-coding RNA responses has been more limited until recently. This review covers what is known regarding host cell non-coding RNA responses in alphavirus infections and highlights gaps in the knowledge that future research should address.


Asunto(s)
Infecciones por Alphavirus , Alphavirus , Encefalitis , Animales , Humanos , Alphavirus/genética , Artralgia , ARN no Traducido/genética
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