Arenavirus Variations Due to Host-Specific Adaptation

Zapata, Juan Carlos; Salvato, María S.

doi:10.3390/v5010241

Cited by 55 publications

(57 citation statements)

References 182 publications

(180 reference statements)

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“…The selection of changes varies with each host, suggesting that the virus sequence adapts to a specific host molecule (Table 4). Changes in GP were very close to the cleavage site (residue 260) (18), changes in NP were either close to the ssRNA binding site (residue 171) in the N domain or close to the immune evasion and Z protein binding sites (residues 59, 223, 341, and 551) in the C domain (18), and changes in L were close to the endonuclease domain (residue 266) or to the globular domain (1572). Protein prediction analysis showed that those mutations, at the amino acid level, induced structural changes in GP and NP (18).…”

Section: Resultsmentioning

confidence: 99%

Genetic Variation In Vitro and In Vivo of an Attenuated Lassa Vaccine Candidate

Zapata

Goicochea

Nadai

et al. 2014

J Virol

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The attenuated Lassa vaccine candidate ML29 is a laboratory-produced reassortant between Lassa and Mopeia viruses, two Old World arenaviruses that differ by 40% in nucleic acid sequence. In our previous studies, ML29 elicited sterilizing immunity against Lassa virus challenge in guinea pigs and marmosets and virus-specific cell-mediated immunity in both simian immunodeficiency virus (SIV)-infected and uninfected rhesus macaques. Here, we show that ML29 is stable after 12 passages in vitro without losing its plaque morphology or its attenuated phenotype in suckling mice. Additionally, we used deep sequencing to characterize the viral population comprising the original stock of ML29, the stock of ML29 after 12 passages in Vero cells, and the ML29 isolates obtained from vaccinated animals. Twenty-seven isolates bore approximately 77 mutations that exceeded 20% of the single-nucleotide polymorphism (SNP) changes at any single locus. Of these 77 mutations, 5 appeared to be host specific, for example, appearing in mice but not in primates. None of these mutations were reversions of ML29 to the sequences of the parental Lassa and Mopeia viruses. The host-specific mutations indicate viral adaptations to virus-host interactions, and such interactions make reasonable targets for antiviral approaches. Variants capable of chronic infection did not emerge from any of the primate infections, even in immune-deficient animals, indicating that the ML29 reassortant is reasonably stable in vivo. In conclusion, the preclinical studies of ML29 as a Lassa virus vaccine candidate have been advanced, showing high levels of protection in nonhuman primates and acceptable stability both in vitro and in vivo.

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Section: Resultsmentioning

confidence: 99%

Genetic Variation In Vitro and In Vivo of an Attenuated Lassa Vaccine Candidate

Zapata

Goicochea

Nadai

et al. 2014

J Virol

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“…Los análisis filogenéticos a partir de las secuencias en estudio indicaron que los virus del género Arenavirus se agruparon formando dos clados independientes constituidos por, al menos, 25 especies, y por los virus del serocomplejo Tacaribe y Lassa-coriomeningitis linfocítica, lo cual coincide con lo evidenciado por Zapata, et al (5). En el árbol se observa que las secuencias de Sincelejo conformaron un grupo monofilético con altos valores de soporte de la rama, cuyo ancestro común está relacionado con el ancestro que dio origen a los LCMV, lo cual demuestra la identidad de estos virus.…”

Section: Discussionunclassified

“…Estos agentes se han clasificado de acuerdo con sus propiedades antigénicas, en dos grupos: el complejo serológico Tacaribe, el cual incluye virus autóctonos del Nuevo Mundo, y el complejo serológico LassaCoriomeningitis Linfocítica, conformado por virus autóctonos de África y por el virus de la coriomeningitis linfocítica (LCMV), conocidos como el grupo del Viejo Mundo (3)(4)(5).…”

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First evidence of Lymphocytic Choriomeningitis virus (Arenaviruses) infection in Mus musculus rodents captured in the urban area of the municipality of Sincelejo-Sucre, Colombia

et al. 2016

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Contribución de los autores:Anaís Castellar: revisión de la literatura científica, recolección y análisis de datos y redacción del manuscrito Marco Guevara y Esteban Arroyave: trabajo de campo y organización de los datos Juan D. Rodas y Andrés Londoño: trabajo de laboratorio, asesoría en la revisión y aportes a la discusión Francisco J. Díaz: revisión crítica y asesoría del contenido, aportes a la discusión y análisis filogenéticos. Silvana Levis: donación de reactivos no comerciales y asesoría en los ensayos, revisión crítica y aportes a la discusión Pedro J. Blanco: contribución en el diseño del estudio, participación en la fase de campo y revisión crítica del manuscrito Results: We found a 10% seroprevalence (8/80) and the viral genome was detected in 16 brain samples; the alignment (BLAST) and the phylogenetic analysis (MrBayes, version 3.2.2) confirmed the presence of the lymphocytic choriomeningitis virus. Conclusion:The results indicated that human infection with the lymphocytic choriomeningitis virus in humans could occur in the urban area of Sincelejo, although no cases have been reported so far.

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“…Animals were defined as having reached terminal points either when their body weight decreased by Ͼ30% compared to a nomogram or if the rectal temperature fell below 38°C in addition to body weight loss. Statistical analyses of the survival curves were performed using the log-rank (Mantel-Cox) 2 test and/or the Fisher's exact test. The statistical significance of duration of fever was analyzed using the Student t test.…”

Section: F F L L L C G G R S C T M G Q I V T M F F E a L L P H I I I mentioning

confidence: 99%

“…A renaviruses can cause neurologic or hemorrhagic fever diseases in humans, and few preventive or therapeutic measures are available (1,2). The most significant arenavirus pathogen is Lassa fever virus (LASV), which causes infections that are endemic to many countries in West Africa, with an estimated 500,000 cases resulting in ϳ5,000 deaths annually (3).…”

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confidence: 99%

Characterization of the Glycoprotein Stable Signal Peptide in Mediating Pichinde Virus Replication and Virulence

Shao

et al. 2016

J Virol

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Arenaviruses can cause lethal hemorrhagic fevers in humans with few preventative and therapeutic measures. The arenaviral glycoprotein stable signal peptide (SSP) is unique among signal peptides in that it is an integral component of the mature glycoprotein complex (GPC) and plays important roles not only in GPC expression and processing but also in the membrane fusion process during viral entry. Using the Pichinde virus (PICV) reverse genetics system, we analyzed the effects of alanine substitutions at many conserved residues within the SSP on viral replication in cell culture and in a guinea pig infection model. Our data showed that the K33A, F49A, and C57A mutations abolished GPC-mediated cell entry and therefore could not allow for the generation of viable recombinant viruses, demonstrating that these residues are essential for the PICV life cycle. The G2A mutation caused a marked reduction of cell entry at the membrane fusion step, and while this mutant virus was viable, it was significantly attenuated in vitro and in vivo. The N20A mutation also reduced membrane fusion activity and viral virulence in guinea pigs, but it did not significantly affect cell entry or viral growth in cell culture. Two other mutations (N37A and R55A) did not affect membrane fusion or viral growth in vitro but significantly reduced viral virulence in vivo. Taken together, our data suggest that the GPC SSP plays an essential role in mediating viral entry and also contributes to viral virulence in vivo. IMPORTANCESeveral arenaviruses, such as Lassa fever virus, can cause severe and lethal hemorrhagic fever diseases with high mortality and morbidity, and no FDA-approved vaccines or therapies are currently available. Viral entry into cells is mediated by arenavirus GPC that consists of an SSP, the receptor-binding GP1, and transmembrane GP2 protein subunits. Using a reverse genetics system of a prototypic arenavirus, Pichinde virus (PICV), we have shown for the first time in the context of virus infections of cell culture and of guinea pigs that the SSP plays an essential role in mediating the membrane fusion step as well as in other yet-to-be-determined processes during viral infection. Our study provides important insights into the biological roles of GPC SSP and implicates it as a good target for the development of antivirals against deadly human arenavirus pathogens.A renaviruses can cause neurologic or hemorrhagic fever diseases in humans, and few preventive or therapeutic measures are available (1, 2). The most significant arenavirus pathogen is Lassa fever virus (LASV), which causes infections that are endemic to many countries in West Africa, with an estimated 500,000 cases resulting in ϳ5,000 deaths annually (3). Except for Junin virus (JUNV), which has a vaccine, Candid#1, used only in Argentina, no licensed vaccine for human use is currently available for any other arenaviruses. Therapeutic options are limited and depend mainly on supportive care. Ribavirin, a nonspecific antiviral compound, has shown some efficacy ...

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Arenavirus Variations Due to Host-Specific Adaptation

Cited by 55 publications

References 182 publications

Genetic Variation In Vitro and In Vivo of an Attenuated Lassa Vaccine Candidate

Genetic Variation In Vitro and In Vivo of an Attenuated Lassa Vaccine Candidate

First evidence of Lymphocytic Choriomeningitis virus (Arenaviruses) infection in Mus musculus rodents captured in the urban area of the municipality of Sincelejo-Sucre, Colombia

Characterization of the Glycoprotein Stable Signal Peptide in Mediating Pichinde Virus Replication and Virulence

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