Viral Load and Cell Tropism During Early Latent Equid Herpesvirus 1 Infection Differ Over Time in Lymphoid and Neural Tissue Samples From Experimentally Infected Horses.
Abstract: Upper respiratory tract infections with Equid Herpesvirus 1 (EHV-1) typically result in a peripheral blood mononuclear cell-associated viremia, which can lead to vasculopathy in the central nervous system. Primary EHV-1 infection also likely establishes latency in trigeminal ganglia (TG) via retrograde axonal transport and in respiratory tract-associated lymphatic tissue. However, latency establishment and reactivation are poorly understood. To characterize the pathogenesis of EHV-1 latency establishment and maintenance, two separate groups of yearling horses were experimentally infected intranasally with EHV-1, strain Ab4, and euthanized 30 days post infection (dpi), ( = 9) and 70 dpi ( = 6). During necropsy, TG, sympathetic trunk (ST), retropharyngeal and mesenteric lymph nodes (RLn, MesLn) and kidney samples were collected. Viral DNA was detected by quantitative PCR (qPCR) in TG, ST, RLn, and MesLn samples in horses 30 and 70 dpi. The number of positive TG, RLn and MesLn samples was reduced when comparing horses 30 and 70 dpi and the viral copy number in TG and RLn significantly declined from 30 to 70 dpi. EHV-1 late gene glycoprotein B reverse transcriptase PCR and IHC results for viral protein were consistently negative, thus lytic replication was excluded in the present study. Mild inflammation could be detected in all neural tissue samples and inflammatory infiltrates mainly consisted of CD3+ T-lymphocytes (T-cells), frequently localized in close proximity to neuronal cell bodies. To identify latently infected cell types, hybridization (ISH, RNAScope®) detecting viral DNA was used on selected qPCR- positive neural tissue sections. In ganglia 30 dpi, EHV-1 ISH signal was located in the neurons of TG and ST, but also in non-neuronal support or interstitial cells surrounding the neuron. In contrast, distinct EHV-1 signal could only be observed in neurons of TG 70 dpi. Overall, detection of latent EHV-1 in abdominal tissue samples and non-neuronal cell localization suggests, that EHV-1 uses T-cells during viremia as alternative route toward latency locations in addition to retrograde neuronal transport. We therefore hypothesize that EHV-1 follows the same latency pathways as its close relative human pathogen Varicella Zoster Virus.
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The study investigates how Equid Herpesvirus 1 (EHV-1), a virus causing upper respiratory tract infections in horses, establishes and maintains latency in different tissues over time. The researchers examined tissues from horses experimentally infected with EHV-1 at 30 and 70 days post-infection, and suggested the virus could use T-cells to reach latency locations.
Methodology and Experimental Design
The researchers experimentally infected two groups of yearling horses intranasally with EHV-1, strain Ab4. Post-infection at 30 and 70 days, the horses were euthanized and samples from various tissues were collected for analysis.
The samples examined included trigeminal ganglia (TG), sympathetic trunk (ST), retropharyngeal and mesenteric lymph nodes (RLn, MesLn), and kidneys.
They detected viral DNA in these samples using quantitative PCR (qPCR) and conducted additional tests to identify latently infected cell types.
Results and Findings
Viral DNA was detected in all types of samples in horses at both 30 and 70 days post-infection. However, the number of samples testing positive and the viral copy number declined from 30 to 70 days.
Despite the presence of viral DNA, there were no signs of active viral replication.
They found mild inflammation in all neural tissue samples. CD3+ T-cells, a type of immune cell, were frequently located close to neuronal cell bodies.
EHV-1 detection patterns in the TG and ST samples suggested that the virus initially targets a variety of cells (neuronal and non-neuronal), but later on only targets neurons, especially at 70 days post-infection.
Conclusions and Implications
The findings suggest that EHV-1 may use T-cells during the viremic phase (when the virus is present in the bloodstream) to reach various latency locations, in addition to using retrograde neuronal transport.
The researchers hypothesize that EHV-1 follows similar latency pathways as the Varicella Zoster Virus, a human pathogen closely related to EHV-1.
The findings may shed light on the pathogenesis of EHV-1 infection and the mechanisms underlying viral latency, which could inform future therapeutic strategies.
Cite This Article
APA
Giessler KS, Samoilowa S, Soboll Hussey G, Kiupel M, Matiasek K, Sledge DG, Liesche F, Schlegel J, Fux R, Goehring LS.
(2020).
Viral Load and Cell Tropism During Early Latent Equid Herpesvirus 1 Infection Differ Over Time in Lymphoid and Neural Tissue Samples From Experimentally Infected Horses.
Front Vet Sci, 7, 621.
https://doi.org/10.3389/fvets.2020.00621
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