Abstract
B virus (Macacine herpesvirus 1), a simplex virus endemic in macaques, causes encephalitis, encephalomyelitis, and death in 80% of untreated zoonotically infected humans with delayed or no treatment. Here we report a significant difference in PI3K/Akt-dependent apoptosis between B virus infected human and macaque dermal fibroblasts. Our data show that B virus infection in either human or macaque fibroblasts results in activation of Akt via PI3K and this activation does not require viral de novo protein synthesis. Inhibition of PI3K with LY294002 results in a significant reduction of viral titers in B virus infected macaque and human fibroblasts with only a modest difference in the reduction of virus titers between the two cell types. We, therefore, tested the hypothesis that B virus results in the phosphorylation of Akt (S473), which prevents apoptosis, enhancing virus replication in B virus infected macaque dermal fibroblasts. We observed markers of intrinsic apoptosis when PI3K activation of Akt was inhibited in B virus infected macaque cells, while, these apoptotic markers were absent in B virus infected human fibroblasts under the same conditions. From these data we suggest that PI3K activates Akt in B virus infected macaque and human fibroblasts, but this enhances virus replication in macaque fibroblast cells by blocking apoptosis.
Highlights
B virus, belongs to the family Herpesviridae, and is relatively innocuous in macaques where coevolution of the virus and host have transpired over millions of years [1, 2]
B virus infection induces the phosphorylation of Akt at serine 473 in both macaque and human fibroblast cells
Understanding the differences that exist in the virus: host cell interactions between different species help in developing interventions to control the deadly B virus infection
Summary
B virus (herpes B virus, Macacine herpesvirus 1), belongs to the family Herpesviridae, and is relatively innocuous in macaques where coevolution of the virus and host have transpired over millions of years [1, 2]. Zoonotic infection with B virus, on the other hand, results more commonly in severe disease with encephalitis, encephalomyelitis, ascending paralysis, and death in 80% of individuals without timely antiviral intervention [3, 4]. Co-evolution of a host and pathogen generally ensures selection of a kind of symbiosis between host and pathogen, whereas emergence of a pathogen in permissive foreign hosts can cause havoc in the absence of coevolution and selection opportunities. Understanding the differences in virus: host cell interactions between natural versus foreign hosts provides insight into mechanisms that can be exploited for development of effective therapeutics/interventions.
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