Lyssavirus phosphoproteins increase mitochondrial complex I activity and levels of reactive oxygen species

Kammouni, Wafa; Wood, Heidi; Jackson, Alan C.

doi:10.1007/s13365-017-0550-z

Cited by 13 publications

(5 citation statements)

References 35 publications

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“…For example, M protein’s apparent modulation of the DDR in the absence of DNA damage might produce a protective environment against virus-induced DNA damage. Indeed, previous studies have indicated that NiV and other mononegaviruses, such as rabies virus, can induce reactive oxygen species (ROS), which can cause DNA damage 39 , 40 . Intriguingly, sequencing of bat genomes, including Pteropodid bats (the natural reservoir of HeV, NiV, lyssaviruses and many other highly pathogenic viruses) revealed that many DNA-damage checkpoint genes have been positively selected for 41 , perhaps to protect bat cells against damage by the large amounts of ROS generated during flight.…”

Section: Discussionmentioning

confidence: 99%

Viral regulation of host cell biology by hijacking of the nucleolar DNA-damage response

et al. 2018

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Recent studies indicate that nucleoli play critical roles in the DNA-damage response (DDR) via interaction of DDR machinery including NBS1 with nucleolar Treacle protein, a key mediator of ribosomal RNA (rRNA) transcription and processing. Here, using proteomics, confocal and single molecule super-resolution imaging, and infection under biosafety level-4 containment, we show that this nucleolar DDR pathway is targeted by infectious pathogens. We find that the matrix proteins of Hendra virus and Nipah virus, highly pathogenic viruses of the Henipavirus genus in the order Mononegavirales, interact with Treacle and inhibit its function, thereby silencing rRNA biogenesis, consistent with mimicking NBS1–Treacle interaction during a DDR. Furthermore, inhibition of Treacle expression/function enhances henipavirus production. These data identify a mechanism for viral modulation of host cells by appropriating the nucleolar DDR and represent, to our knowledge, the first direct intranucleolar function for proteins of any mononegavirus.

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Section: Discussionmentioning

confidence: 99%

Viral regulation of host cell biology by hijacking of the nucleolar DNA-damage response

et al. 2018

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“…GPR17 is activated by RABV infection and mediates apoptosis through BAK pathway to inhibit viral replication In addition, some researchers found that RABV N, P, and G proteins were present in mitochondria using proteomics analysis. Kammouni et al 134,135 found that P protein of RABV street strain and Mokola strain could enhance the activity of mitochondrial complex I and increase the level of ROS. The amino acids 139-172 of P protein could interact with mitochondrial respiratory chain complex I (MRCC-I), and S162 and S166 are the critical sites in P protein for this interaction.…”

Section: Mitochondrial Dys Fun C Tion In the Pro Ce Ss Of R Abv Repli...mentioning

confidence: 99%

Regulation of innate immune responses by rabies virus

Zhang

Huang

Song

et al. 2022

Anim Models and Exp Med

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Rabies is one of the oldest zoonotic diseases caused by rabies virus (RABV). It has been a global concern because after the symptoms of rabies appear, the mortality rate is close to 100%, and it ultimately leads to death; only a very few cases survive with serious sequelae.Although prevention and control of rabies has greatly improved globally and rabies cases are extremely rare in developed countries and regions, 1,2 it is still at a high level in many developing countries and less-developed countries, mainly concentrated in Africa and Asia. [3][4][5][6][7][8][9][10][11][12][13][14][15] According to the World Health Organization report in 2017, about 59 000 people die of rabies every year. Except for vaccination and emergency treatment with a specific antiserum after exposure, [16][17][18] there are no effective drugs for rabies. 19 The pathogenic mechanism of RABV and the relationship between the virus and host immune response are not thoroughly understood, leading to a lag in the development of therapeutic drugs.RABV has a wide host range with the ability to infect almost all warm-blooded animals. RABV is an enveloped, nonsegmented, single-stranded, negative-sense RNA virus and is classified in the

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“…For example, mitochondrial redox state and electron transport activity can be restored by reducing HCV replication in full genomic HCV replicon cells [14]. The phosphoproteins of lyssaviruses, such as rabies virus (RABV) and Mokola (MOK) virus, interact with mitochondrial respiratory chain complex I to cause mitochondrial dysfunction and increase the generation of ROS and oxidative stress [15]. Ebermann et al demonstrated that increasing the activity of mitochondrial respiratory chain complexes I and III inhibited coxsackievirus B3 (CVB3) replication [16].…”

Section: Introductionmentioning

confidence: 99%

The host cellular protein Ndufaf4 interacts with the vesicular stomatitis virus M protein and affects viral propagation

Pan

Wang

2020

Preprint

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Background: Vesicular stomatitis virus (VSV) is an archetypal member of Mononegavirales which causes important diseases in cattle, horses and pigs. The matrix protein (M) of VSV plays critical roles in the replication, assembly/budding and pathogenesis of VSV. To further investigate the role of M during viral growth, we used a two-hybrid system to screen for host factors that interact with the M protein. Results: Here, NADH: ubiquinone oxidoreductase complex assembly factor 4 (Ndufaf4) was identified as an M-binding partner, and this interaction was confirmed by yeast cotransformation and GST pulldown assays. The globular domain of M was mapped and shown to be critical for the M-Ndufaf4 interaction. Two double mutations (E156A/H157A, D180A/E181A) in M impaired the M-Ndufaf4 interaction. Overexpression of Ndufaf4 inhibited VSV propagation, and knockdown of Ndufaf4 by short hairpin RNA (shRNA) markedly promoted VSV replication. Finally, we also demonstrate that the anti-VSV effect of Ndufaf4 is independent of activation of the type I IFN response. These results indicated that Ndufaf4 might exploit other mechanisms to affect VSV replication. Conclusions: In summary, we identify Ndufaf4 as a potential target for the inhibition of VSV propagation. These results provided further insight into the study of VSVpathogenesis.

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Lyssavirus phosphoproteins increase mitochondrial complex I activity and levels of reactive oxygen species

Cited by 13 publications

References 35 publications

Viral regulation of host cell biology by hijacking of the nucleolar DNA-damage response

Viral regulation of host cell biology by hijacking of the nucleolar DNA-damage response

Regulation of innate immune responses by rabies virus

The host cellular protein Ndufaf4 interacts with the vesicular stomatitis virus M protein and affects viral propagation

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