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Reactive Oxygen Species Hydrogen Peroxide Mediates Kaposi's
Sarcoma-Associated Herpesvirus Reactivation from Latency


Kaposi's sarcoma-associated herpesvirus (KSHV) establishes a latent

infection in the host following an acute infection. Reactivation from latency

contributes to the development of KSHV-induced malignancies, which include

Kaposi's sarcoma (KS), the most common cancer in untreated AIDS patients,

primary effusion lymphoma and multicentric Castleman's disease. However,

the physiological cues that trigger KSHV reactivation remain unclear. Here, we

show that the reactive oxygen species (ROS) hydrogen peroxide

(H2O2) induces KSHV reactivation from latency through

both autocrine and paracrine signaling. Furthermore, KSHV spontaneous lytic

replication, and KSHV reactivation from latency induced by oxidative stress,

hypoxia, and proinflammatory and proangiogenic cytokines are mediated by

H2O2. Mechanistically, H2O2

induction of KSHV reactivation depends on the activation of mitogen-activated

protein kinase ERK1/2, JNK, and p38 pathways. Significantly,

H2O2 scavengers N-acetyl-L-cysteine (NAC), catalase

and glutathione inhibit KSHV lytic replication in culture. In a mouse model of

KSHV-induced lymphoma, NAC effectively inhibits KSHV lytic replication and

significantly prolongs the lifespan of the mice. These results directly relate

KSHV reactivation to oxidative stress and inflammation, which are physiological

hallmarks of KS patients. The discovery of this novel mechanism of KSHV

reactivation indicates that antioxidants and anti-inflammation drugs could be

promising preventive and therapeutic agents for effectively targeting KSHV

replication and KSHV-related malignancies.


Vyšlo v časopise: Reactive Oxygen Species Hydrogen Peroxide Mediates Kaposi's Sarcoma-Associated Herpesvirus Reactivation from Latency. PLoS Pathog 7(5): e32767. doi:10.1371/journal.ppat.1002054
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002054

Souhrn

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes a latent

infection in the host following an acute infection. Reactivation from latency

contributes to the development of KSHV-induced malignancies, which include

Kaposi's sarcoma (KS), the most common cancer in untreated AIDS patients,

primary effusion lymphoma and multicentric Castleman's disease. However,

the physiological cues that trigger KSHV reactivation remain unclear. Here, we

show that the reactive oxygen species (ROS) hydrogen peroxide

(H2O2) induces KSHV reactivation from latency through

both autocrine and paracrine signaling. Furthermore, KSHV spontaneous lytic

replication, and KSHV reactivation from latency induced by oxidative stress,

hypoxia, and proinflammatory and proangiogenic cytokines are mediated by

H2O2. Mechanistically, H2O2

induction of KSHV reactivation depends on the activation of mitogen-activated

protein kinase ERK1/2, JNK, and p38 pathways. Significantly,

H2O2 scavengers N-acetyl-L-cysteine (NAC), catalase

and glutathione inhibit KSHV lytic replication in culture. In a mouse model of

KSHV-induced lymphoma, NAC effectively inhibits KSHV lytic replication and

significantly prolongs the lifespan of the mice. These results directly relate

KSHV reactivation to oxidative stress and inflammation, which are physiological

hallmarks of KS patients. The discovery of this novel mechanism of KSHV

reactivation indicates that antioxidants and anti-inflammation drugs could be

promising preventive and therapeutic agents for effectively targeting KSHV

replication and KSHV-related malignancies.


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Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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