TY - JOUR
T1 - mTORC2 confers neuroprotection and potentiates immunity during virus infection
AU - Suryawanshi, Rahul K.
AU - Patil, Chandrashekhar D.
AU - Agelidis, Alex
AU - Koganti, Raghuram
AU - Ames, Joshua M.
AU - Koujah, Lulia
AU - Yadavalli, Tejabhiram
AU - Madavaraju, Krishnaraju
AU - Shantz, Lisa M.
AU - Shukla, Deepak
N1 - Funding Information:
We are grateful to Dr. Nissim Hay for FoxO3a−/− cells. This work was supported by the National Institutes of Health RO1 grants EY029426, AI139768, EY024710 (to DS) and a NEI core grant (EY001792) and Illinois society for prevention of blindness. This content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Herpes simplex virus type-1 (HSV-1) causes ocular and orofacial infections. In rare cases, HSV-1 can cause encephalitis, which leads to permanent brain injuries, memory loss or even death. Host factors protect humans from viral infections by activating the immune response. However, factors that confer neuroprotection during viral encephalitis are poorly understood. Here we show that mammalian target of rapamycin complex 2 (mTORC2) is essential for the survival of experimental animals after ocular HSV-1 infection in vivo. We find the loss of mTORC2 causes systemic HSV-1 infection due to defective innate and adaptive immune responses, and increased ocular and neuronal cell death that turns lethal for the infected mice. Furthermore, we find that mTORC2 mediated cell survival channels through the inactivation of the proapoptotic factor FoxO3a. Our results demonstrate how mTORC2 potentiates host defenses against viral infections and implicate mTORC2 as a necessary factor for survival of the infected host.
AB - Herpes simplex virus type-1 (HSV-1) causes ocular and orofacial infections. In rare cases, HSV-1 can cause encephalitis, which leads to permanent brain injuries, memory loss or even death. Host factors protect humans from viral infections by activating the immune response. However, factors that confer neuroprotection during viral encephalitis are poorly understood. Here we show that mammalian target of rapamycin complex 2 (mTORC2) is essential for the survival of experimental animals after ocular HSV-1 infection in vivo. We find the loss of mTORC2 causes systemic HSV-1 infection due to defective innate and adaptive immune responses, and increased ocular and neuronal cell death that turns lethal for the infected mice. Furthermore, we find that mTORC2 mediated cell survival channels through the inactivation of the proapoptotic factor FoxO3a. Our results demonstrate how mTORC2 potentiates host defenses against viral infections and implicate mTORC2 as a necessary factor for survival of the infected host.
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U2 - 10.1038/s41467-021-26260-5
DO - 10.1038/s41467-021-26260-5
M3 - Article
C2 - 34650053
AN - SCOPUS:85117372504
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 6020
ER -