Ineffectual immunity in a resurrected mouse model of persistent viremia
Data files
Apr 03, 2025 version files 25.79 KB
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LDV_Immunity_-_DRYAD.xlsx
25.05 KB
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README.md
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Abstract
Viruses that establish persistent (i.e., chronic) infection have evolved sophisticated strategies to avoid clearance by the host immune system. This is particularly true for viruses that infect immunocompetent mammals and sustain high infectious burdens in body sites under intense immune surveillance (i.e., the blood, a.k.a., “viremia”). Historically, lymphocytic choriomeningitis virus (LCMV) infection of laboratory mice has served as a powerful model to understand mechanisms of failed immunity, but other viruses may have unique and underappreciated persistence strategies. Here, we resurrect a bygone model of viral persistence––lactate dehydrogenase-elevating virus (LDV)––and use modern transgenic mouse technologies to investigate various aspects of anti-viral immunity. We find that interferons have a modest impact on LDV replication, with interferon-alpha blunting LDV viremia in the acute phase of the infection and interferon-gamma reducing LDV viral loads in the chronic phase of infection, but only when paired with an intact interferon-alpha response. Adaptive immunity, assessed in Rag-knockout mice, had only a modest impact on LDV viremia, and only during the sub-acute phase of infection. Mice lacking the critical immune checkpoint molecule PD-1 showed no signs of disease and supported LDV viral loads at levels equivalent to their wild-type counterparts. Altogether, these results point to a novel and highly effective mechanism of persistence that is minimally impacted by conventional aspects of anti-viral immunity or immune exhaustion––a rarity among persistent viruses. Given the relative paucity of chronic infection models in the laboratory mouse, LDV infection may be useful for exploring unique modes of immune system failure.
Dataset DOI: 10.5061/dryad.2ngf1vj0v
Description of the data and file structure
Each tab in the .csv file corresponds to the data from a figure in the corresponding manuscript. LDV= lactate dehydrogenase elevating virus of mice, Plagemann strain. PFU= plaque forming units. RT-qPCR= reverse transcription quantitative polymerase chain reaction. All blank cells are left intentionally blank.
Figure 1: LDV viral loads in wild-type mice over time
Figure 2: LDV viral loads in mice with different immune-gene deficiencies over time
Figure 3: Weight loss and LDV viral loads in mice lacking the immune checkpoint inhibitor PD-1.