Nei-like DNA glycosylase 2 selectively antagonizes interferon-β expression upon respiratory syncytial virus infection

Pan, Lang; Xue, Yaoyao; Wang, Ke; Zheng, Xu; Islam, Azharul; Tapryal, Nisha; Chakraborty, Anirban; Bácsi, Attila; Ba, Xueqing; Hazra, Tapas K.; Boldogh, István

doi:10.1016/j.jbc.2023.105028

Cited by 5 publications

(1 citation statement)

References 47 publications

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“…We reported earlier that NEIL2 acts as a repressor of NF-κB, a transcriptional activator of proinflammatory genes such as TNFα , IL6 and IL1β 36 . We have also reported recently, that rNEIL2 inhibits IFN-β mediated proinflammatory gene expression by antagonizing NF-κB’s access to IFN-β promoter, early after respiratory syncytial virus infection 54 . In the present study, we have demonstrated that transduction of rNEIL2 in A549-ACE2 cells significantly inhibited SARS-CoV-2 induced TNFα , IL6, IL1β, CCL2, CCL3 and CXCL10 expression, further confirming anti-inflammatory role of NEIL2.…”

Section: Discussionmentioning

confidence: 54%

The DNA glycosylase NEIL2 is protective during SARS-CoV-2 infection

Tapryal,

Chakraborty,

Saha

et al. 2023

Nat Commun

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SARS-CoV-2 infection-induced aggravation of host innate immune response not only causes tissue damage and multiorgan failure in COVID-19 patients but also induces host genome damage and activates DNA damage response pathways. To test whether the compromised DNA repair capacity of individuals modulates the severity of COVID-19 infection, we analyze DNA repair gene expression in publicly available patient datasets and observe a lower level of the DNA glycosylase NEIL2 in the lungs of severely infected COVID-19 patients. This observation of lower NEIL2 levels is further validated in infected patients, hamsters and ACE2 receptor-expressing human A549 (A549-ACE2) cells. Furthermore, delivery of recombinant NEIL2 in A549-ACE2 cells shows decreased expression of proinflammatory genes and viral E-gene, as well as lowers the yield of viral progeny compared to mock-treated cells. Mechanistically, NEIL2 cooperatively binds to the 5’-UTR of SARS-CoV-2 genomic RNA to block viral protein synthesis. Collectively, these data strongly suggest that the maintenance of basal NEIL2 levels is critical for the protective response of hosts to viral infection and disease.

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Section: Discussionmentioning

confidence: 54%

The DNA glycosylase NEIL2 is protective during SARS-CoV-2 infection

Tapryal,

Chakraborty,

Saha

et al. 2023

Nat Commun

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NEIL1 block IFN-β production and enhance vRNP function to facilitate influenza A virus proliferation

Zhang,

Li,

Sun

et al. 2024

npj Viruses

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Assessment of genome complementarity in three beef-on-dairy crossbreds reveals sire-specific effects on production traits with comparable rates of genomic inbreeding reduction

Lindtke,

Lerch,

Morel

et al. 2024

BMC Genomics

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Background Crossbreeding beef bulls with dairy cows can improve the economic value and fitness of calves not entering dairy production owing to increased meat yield and heterosis. However, outcrossing might reduce the dosage of alleles that confer local adaptation or result in a higher risk of dystocia due to increased calf size. Given the clear phenotypic differences between beef breeds, the varying phylogenetic distances between beef and dairy breeds, and the genomic variations within breeds, the attainable economic and fitness gains of calves will strongly depend on the selection of sires for crossing. Thus, the aim of this study was to assess genome complementarity between Angus (AAN), Limousin (LIM), or Simmental (SIM) beef bulls and Brown Swiss (BSW) dairy cows by quantifying genomic inbreeding reduction in F1 crosses and identifying genes potentially under BSW-specific selection that might be affected by outcrossing. ResultsLow-pass sequencing data from 181 cows, 34 bulls, and 301 of their F1 progeny, and body weight and carcass composition measurements of 248 F1s were obtained. The high genomic inbreeding levels detected in the BSW cows were substantially reduced in the crossbreds, with only minor differences between the sire breeds. In the BSW cows, 585 candidate genes under selection were identified, overrepresenting genes associated with milk, meat and carcass, and production traits. Only a few genes were strongly differentiated at nonsynonymous variants between the BSW and beef breeds, including four tightly clustered genes (FAM184B, NCAPG, DCAF16, and LCORL) nearly fixed for alternate alleles in the BSW cows but mostly heterozygous or homozygous for the reference alleles in the AAN and LIM bulls. The alternate allele dosage at these genes significantly correlated with reduced carcass weight and protein mass in F1s. Conclusion Some of the few genes that were highly divergent between the BSW and beef breeds at nonsynonymous variants were likely under strong selection for reduced carcass weight in the BSW breed, potentially due to trade-offs between beef and dairy productions. As alleles with opposing effects still segregate in beef cattle, marker-assisted selection of mating pairs may be used to modulate the desired phenotypes and simultaneously decrease genomic inbreeding.

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Nei-like DNA glycosylase 2 selectively antagonizes interferon-β expression upon respiratory syncytial virus infection

Cited by 5 publications

References 47 publications

The DNA glycosylase NEIL2 is protective during SARS-CoV-2 infection

The DNA glycosylase NEIL2 is protective during SARS-CoV-2 infection

NEIL1 block IFN-β production and enhance vRNP function to facilitate influenza A virus proliferation

Assessment of genome complementarity in three beef-on-dairy crossbreds reveals sire-specific effects on production traits with comparable rates of genomic inbreeding reduction

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