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E. M. Cantin, R. Chandran, Q. Xing; Neither B or T Cells Are Mandatory for Maintainance of HSV Latency. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3876.
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© ARVO (1962-2015); The Authors (2016-present)
To develop a model to investigate the requirement for T cells in maintenance of HSV latency and control of reactivated virus.
We have developed a novel model of latency in immunodeficient resistant C57BL/6J (B6) and susceptible 129S6 (129) Rag mice inoculated with HSV 17+ by the corneal route. A single does of intravenous immunoglobulin (IVIG) given 24 post infection (pi) promoted survival with stable latency in 129- and B6-Rag mice inoculated at ≤ 32x LD50 for the respective strains. In contrast, 3 - 4 cycles of treatment with IVIG in combination with a 10 daily injections of ACV was required to achieve stable latency in mice inoculated at ≥ 32x LD50. IVIG protects 129-Rag mice by suppressing both virus replication and pathogenic CNS inflammatory responses, whereas protection of B6-Rag mice involves only the antiviral mechanism.
HSV was efficiently reactivated (>80%) in vitro from trigeminal ganglia (Tgs) of 129- and B6-Rag mice inoculated at all doses (1 -100x LD50) and treated with IVIG at 24 h pi. HSV was undetectable in Tgs from latently infected mice sacrificed random time points after the last IVIG/ACV treatment. However, a few sporadic deaths occurred in mice inoculated at 100x LD50 as a result of spontaneous reactivation. In contrast, hyperthermia induced in vivo reactivation resulted in synchronous development of encephalitis culminating in high mortality for 129-Rag and B6-Rag mice inoculated at 100x LD50’ but not wild type mice inoculated at the same dose or Rag mice inoculated at ≤ 32x LD50.
Latency resulting from physiologically relevant low dose inoculation of HSV can be controlled by innate responses alone whereas high dose inoculations require adaptive immunity to preclude spontaneous reactivation. The threshold of latent HSV genomes required for efficient in vivo reactivation is much higher for B6-Rag compared to 129-Rag mice, which may be related to superior innate mechanisms in B6 mice operating to suppress reactivation. This unique latency model will facilitate further studies of T cell control of HSV latency.
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