Single-stranded RNA viruses activate and hijack host apical DNA damage response kinases for efficient viral replication

Li, Pengcheng; Xu, Chenchen; Zhang, Xiaoyan; Cao, Cheng; Wang, Xuejuan

doi:10.1007/s42764-022-00064-3

Cited by 3 publications

(2 citation statements)

References 13 publications

(13 reference statements)

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“…Throughout human history, there have been several public health crises caused by influenza viruses, such as the Spanish influenza (H1N1) in 1918 [ 18 ], Asian influenza (H2N2) in 1957 [ 19 ], Hong Kong influenza (H3N2) in 1968 [ 20 ], and influenza A in 2009 [ 21 ]. Each pandemic outbreak caused enormous damage to the economies of the affected countries and to human health [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic Study and Metabolite Identification of CAM106 in Rats by Validated UHPLC-MS/MS

Abdulla

Zhao

et al. 2023

Pharmaceuticals

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Given the limitations of existing antiviral drugs and vaccines, there is still an urgent need for new anti-influenza drugs. CAM106, a rupestonic acid derivative, was studied for its potent antiviral activity and showed a favorable inhibitory effect on influenza virus replication. However, many gaps exist in preclinical studies of CAM106. This study focused on the pharmacokinetic profile and metabolites of CAM106 in vivo. An efficient and fast bioanalytical method was successfully developed and validated for the quantitation of CAM106 in rat plasma. A mobile phase aqueous solution (A, containing 0.1% formic acid) and acetonitrile (B) worked within 0–3.5 min, with 60% B. The mass spectrum scanning mode was the parallel reaction monitoring (PRM) with a resolution of 17,500. The linear range of the method was 2.13–1063.83 ng/mL. The validated method was applied to a pharmacokinetic study in rats. The matrix effects ranged from 93.99% to 100.08% and the recovery ranged from 86.72% to 92.87%. The intra- and inter-day precisions were less than 10.24% and the relative error (RE) ranged from −8.92% to 7.1%. The oral bioavailability of CAM106 was 1.6%. Thereafter, its metabolites in rats were characterized using high-resolution mass spectrometry. The isomers M7-A, M7-B, M7-C, and M7-D were well separated. As a result, a total of 11 metabolites were identified in the feces, urine, and plasma of rats. The main metabolic pathways of CAM106 were oxidation, reduction, desaturation, and methylation. The assay was reliable and provided useful information for further clinical studies of CAM106.

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Section: Introductionmentioning

confidence: 99%

Pharmacokinetic Study and Metabolite Identification of CAM106 in Rats by Validated UHPLC-MS/MS

Abdulla

Zhao

et al. 2023

Pharmaceuticals

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“…In ZIKV infection, the induction of the ATM signaling and corresponding S-phase arrest increases viral replication (27). Moreover, both ATM and ATR kinases have been described to be activated by PRRSV infection, colocalize with the viral replication complexes and promote replication (28). How (+)RNA viruses that replicate at the cytosol induce the DNA-damage network remains unclear.…”

Section: Introductionmentioning

confidence: 99%

The host tRNA epitranscriptome: A new player in RNA virus infections

2022

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Viruses completely depend on the host translation machineries to express the viral proteins. Recent data reveal an unprecedented interaction of positive strand RNA ((+)RNA) viruses with the host tRNA epitranscriptome to favor viral protein expression via a specific reprogramming of codon optimality that ultimately favors decoding of the viral codons. We propose that this feature is shared by multiple RNA viruses and that the involved tRNA modifying enzymes represent promising novel targets for the development of broad-spectrum antivirals.

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miR-155 facilitates the synergistic replication between avian leukosis virus subgroup J and reticuloendotheliosis virus by targeting a dual pathway

Xue,

Zhou,

Zhou

et al. 2023

J Virol

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Co-infection of avian leukosis virus subgroup J (ALV-J) and reticuloendotheliosis virus (REV) in poultry flocks induces synergistic replication, which worsens immunosuppression, growth inhibition, and increased mortality. However, the synergistic replication mechanism between ALV-J and REV is still not fully understood. We showed that microRNA-155 (miR-155) targets a dual pathway, PRKCI-MAPK8 and TIMP3-MMP2, which interacts with the U3 region of ALV-J and REV to promote synergistic replication between ALV-J and REV. Initially, we found that the RNA levels of ALV-J and REV increased significantly in ALV-J and REV co-infected cells and tissues compared with mono-infected cells and tissues. Next, miRNAomics showed that ALV-J and REV synergistically increased miR-155 levels. In co-infected cells, miR-155 promoted synergistic replication of ALV-J and REV. All structural proteins of the two viruses activated the expression of miR-155, especially gag proteins, rather than insertional activation. Proteomic study of cells co-infected with ALV-J and REV and transfected with miR-155 indicated that miR-155 directly suppressed PRKCI and TIMP3 and that PRKCI directly prevented MAPK8 expression, while TIMP3 directly interfered MMP2 expression. We also found that MAPK8 and MMP2 co-interacted with ALV-J and REV’s U3 to enhance synergistic replication. In conclusion, ALV-J and REV synergistically activate miR-155, facilitating the synergistic replication of ALV-J and REV by PRKCI-MAPK8 and TIMP3-MMP2 dual-pathway interaction with the U3 region of ALV-J and REV. This discovery will assist in explaining how two retroviruses replicate synergistically. IMPORTANCE The synergy of two oncogenic retroviruses is an essential phenomenon in nature. The synergistic replication of ALV-J and REV in poultry flocks increases immunosuppression and pathogenicity, extends the tumor spectrum, and accelerates viral evolution, causing substantial economic losses to the poultry industry. However, the mechanism of synergistic replication between ALV-J and REV is still incompletely elusive. We observed that microRNA-155 targets a dual pathway, PRKCI-MAPK8 and TIMP3-MMP2, interacting with the U3 region of ALV-J and REV, enabling synergistic replication. This work gives us new targets to modulate ALV-J and REV’s synergistic replication, guiding future research on the mechanism.

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Single-stranded RNA viruses activate and hijack host apical DNA damage response kinases for efficient viral replication

Cited by 3 publications

References 13 publications

Pharmacokinetic Study and Metabolite Identification of CAM106 in Rats by Validated UHPLC-MS/MS

Pharmacokinetic Study and Metabolite Identification of CAM106 in Rats by Validated UHPLC-MS/MS

The host tRNA epitranscriptome: A new player in RNA virus infections

miR-155 facilitates the synergistic replication between avian leukosis virus subgroup J and reticuloendotheliosis virus by targeting a dual pathway

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