Astrovirus reverse genetics systems, a story of success

Sandoval-Jaime, Carlos

doi:10.1016/j.coviro.2020.06.009

Cited by 5 publications

(5 citation statements)

References 58 publications

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“…Recent developments in AstV reverse genetics systems allow for precision engineering and good recovery from expression cell lines [ 56 , 57 ]. Even with the availability of this system, there have not been any reported attempts to engineer the AstV proteins into a therapeutic or vector system.…”

Section: Engineering and Practical Applications Of Astv Structural Proteins And Vlpsmentioning

confidence: 99%

Structural Insights into the Human Astrovirus Capsid

Ykema

Tao

2021

Viruses

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Astroviruses (AstVs) are non-enveloped, positive single-stranded RNA viruses that cause a wide range of inflammatory diseases in mammalian and avian hosts. The T = 3 viral capsid is unique in its ability to infect host cells in a process driven by host proteases. Intercellular protease cleavages allow for viral egress from a cell, while extracellular cleavages allow for the virus to enter a new host cell to initiate infection. High-resolution models of the capsid core indicate a large, exposed region enriched with protease cleavage sites. The virus spike protein allows for binding to target cells and is the major target for naturally occurring and engineered neutralizing antibodies. During maturation, the capsid goes through significant structural changes including the loss of many surface spikes. The capsid interacts with host membranes during the virus life cycle at multiple stages such as assembly, host cell entry and exit. This review will cover recent findings and insights related to the structure of the capsid and its function. Further understanding of the viral capsid structure and maturation process can contribute to new vaccines, gastric therapeutics, and viral engineering applications.

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Section: Engineering and Practical Applications Of Astv Structural Proteins And Vlpsmentioning

confidence: 99%

Structural Insights into the Human Astrovirus Capsid

Ykema

Tao

2021

Viruses

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“…The ability of MLB astroviruses to replicate in Huh7.5.1 cells provides a great advantage for the development of the RG system: A single cell line can be used for both virus rescue and propagation—something that is not possible for other astroviruses with cell tropism restricted to non-transfectable cell lines [ 22 ]. Huh7.5.1 cells were electroporated with transcribed RNAs and incubated for 48 h (MLB2) or 72 h (MLB1) until the appearance of CPE.…”

Section: Resultsmentioning

confidence: 99%

“…HAstV1 RG system requires 2 cell lines to recover infectious particles: the transfection of BHK-21 cells with in vitro transcribed viral RNA and then propagation of the obtained supernatant in the permissive Caco2 cells in the presence of trypsin. Several DNA-based RG systems were developed, including efficient chimeric HAstV1/8 RG system [ 21 , 22 ]; however, all of them relied on 2 cell lines and were limited to classical human astroviruses. So far, RG systems for 2 nonhuman astroviruses were developed: first for the avian astrovirus by using duck astrovirus (DAstV) genome of D51 strain [ 23 ] and second for porcine astrovirus (PAstV1-GX1) [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Attenuation hotspots in neurotropic human astroviruses

et al. 2023

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During the last decade, the detection of neurotropic astroviruses has increased dramatically. The MLB genogroup of astroviruses represents a genetically distinct group of zoonotic astroviruses associated with gastroenteritis and severe neurological complications in young children, the immunocompromised, and the elderly. Using different virus evolution approaches, we identified dispensable regions in the 3′ end of the capsid-coding region responsible for attenuation of MLB astroviruses in susceptible cell lines. To create recombinant viruses with identified deletions, MLB reverse genetics (RG) and replicon systems were developed. Recombinant truncated MLB viruses resulted in imbalanced RNA synthesis and strong attenuation in iPSC-derived neuronal cultures confirming the location of neurotropism determinants. This approach can be used for the development of vaccine candidates using attenuated astroviruses that infect humans, livestock animals, and poultry.

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“…However, the frequency of diarrhea and the degree of fever were not statistically significant. Although the symptoms of HAstV infection are mild and most children recover within a week, virus excretion can be detected for up to 2 weeks after symptoms have cleared 27 . So, we should pay attention to the infectivity of patients even though their symptoms had relieved.…”

Section: Discussionmentioning

confidence: 99%

Molecular and clinical epidemiological features of human astrovirus infections in children with acute gastroenteritis in Shandong province, China

Huang

Wang

Zhang

et al. 2021

Journal of Medical Virology

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Human astrovirus (HAstV) is one of the most common causative agents of acute gastroenteritis in children with an infection rate estimated to range from 2% to 9% worldwide. This study was aimed at investigating the molecular and clinical epidemiological features of human astrovirus infections in children under 5 years old with acute gastroenteritis in Shandong province, China from July 2017 to June 2018. In total, 376 fecal samples and the corresponding clinical information were collected and analyzed. HAstV infections were detected in all age groups with an overall positive rate of 8.51%. In addition to acute diarrhea, the main clinical manifestations were fever, abdominal pain, vomiting, and dehydration, in which fever was the most common complication. Infections could be seen throughout the year with a peak in the colder season. Four genotypes were detected in which HAstV‐1 was the most prevalent genotype with a prevalence of 78.12%, followed by HAstV‐5 (9.38%), MLB‐1 (9.38%), and MLB‐2 (3.12%). HAstV‐1 strains were classified as lineage 1a, 1b, and 1d, in which lineage 1a strains were the most prevalent followed by lineage 1b and lineage 1d strains. All HAstV‐5 strains were classified as lineage 5b and no other lineages were detected. The results showed that HAstV infection was an important cause of acute gastroenteritis among children under 5 years old in Shandong province. Given that their disease spectrum had been broadened, HAstVs should be paid more attention, not only as a causative agent of acute gastroenteritis but also as a potential pathogen of unexpected diseases.

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Astrovirus reverse genetics systems, a story of success

Cited by 5 publications

References 58 publications

Structural Insights into the Human Astrovirus Capsid

Structural Insights into the Human Astrovirus Capsid

Attenuation hotspots in neurotropic human astroviruses

Molecular and clinical epidemiological features of human astrovirus infections in children with acute gastroenteritis in Shandong province, China

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