The P gene of rodent brain-adapted measles virus plays a critical role in neurovirulence

Abstract

In rare cases, measles virus (MV) in children leads to fatal neurological complications such as primary measles encephalitis, post-acute measles encephalitis, subacute sclerosing panencephalitis and measles inclusion-body encephalitis. To investigate the pathogenesis of MV-induced encephalitis, rodent brain-adapted MV strains CAM/RB and CAMR40 were generated. These strains acquired mutations to adapt to the rodent brain during 40 passages in rat brain. However, it is still unknown which genes confer the neurovirulence of MV. We previously established a rescue system for recombinant MVs possessing the backbone of wild-type strain HL, an avirulent strain in mice. In the present study, to identify the genes in CAMR40 that elicit neurovirulence, we generated chimeric recombinant MVs based on strain HL. As a result, recombinant wild-type MV in which the haemagglutinin (H) gene was substituted with that of CAMR40 caused a non-lethal mild disease in mice, while additional substitution of the HL phosphoprotein (P) gene with that of strain CAMR40 caused lethal severe neurological signs comparable to those of CAMR40. These results clearly indicated that, in addition to the H gene, the P gene is required for the neurovirulence of MV CAMR40.

Downregulation of mitochondrial biogenesis by virus infection triggers antiviral responses by cyclic GMP-AMP synthase

“…To further confirm the implication of cGAS in antiviral responses during MeV infection in vivo , we used a rodent brain-adapted strain of MeV (MeV-CAMR40) [ 40 , 41 ]. Knockout mice lacking the RNA sensor-related molecule (MAVS) or DNA sensor molecule (cGAS) were intracerebrally inoculated with the virus, and the survival curve was measured.…”

“…A72-B cells (canine fibroblast cells; kindly provided from Intervet KK Co. Ltd., Japan) were cultured in Eagle’s minimal essential medium supplemented with 10% FCS and 0.3% triptose phosphate broth. MeV-HL and rMV-EGFP [ 18 ] or MeV-CAMR40 [ 41 ] were infected with B95a cells or Vero cells supplemented with 2% FCS, respectively, and harvested by freeze-thawing and sonication when syncytium formation was at its maximum. Strain RSV-A2 was inoculated into HEp-2 cells supplemented with 2% FCS, and 4 days later cells were harvested together with culture medium and sonicated.…”

Measles Encephalitis: Towards New Therapeutics

“…Most of the time, the viral cycle does not seem compromised but the lower expression level of V could contribute to the viral persistence by reduced inhibition of interferon (IFN) response [134]. Is has also been shown that the P gene of the multi-mutated rodent brain-adapted strain CAMR40 is largely involved in neurovirulence, suggesting that MeV P gene could also play a role in CNS infection [135].…”