Japanese Encephalitis Virus Persistence in Porcine Tonsils Is Associated With a Weak Induction of the Innate Immune Response, an Absence of IFNγ mRNA Expression, and a Decreased Frequency of CD4+CD8+ Double-Positive T Cells

Abstract

In humans, Japanese encephalitis virus (JEV) causes a devastating neurotropic disease with high mortality, whereas in pigs, the virus only causes mild symptoms. Besides tropism to the central nervous system, JEV seems to harbor a particular tropism for the tonsils in pigs. This secondary lymphoid organ appears to act as a reservoir for the virus, and we show that it is found up to 21 days post infection at high viral titers. The immune response in the tonsils was studied over time upon intradermal inoculation of pigs. Entry of the virus in the tonsils was accompanied by a significant increase in anti-viral OAS1 and IFNβ mRNA expression. This limited antiviral response was, however, not sufficient to stop JEV replication, and importantly, no IFNγ or innate inflammatory cytokine mRNA expression could be observed. Strikingly, the persistence of JEV in tonsils was also associated with a significant decreased frequency of CD4+CD8+ double-positive T lymphocytes. Furthermore, it is important to note that JEV persistence in tonsils occurred despite a strong induction of the adaptive immune response. JEV-specific antibodies were found after 6 days post infection in serum, and cell-mediated immune responses upon NS3 restimulation of PBMCs from experimentally infected pigs showed that CD4+CD8+ double-positive T cells were found to display the most prominent proliferation and IFNγ production among lymphocyte subtypes. Taken together, these results suggest that an inadequate induction of the innate immune response and the absence of an IFNγ antiviral response contribute to the persistence of JEV in the tonsils and is associated with a decrease in the frequency of CD4+CD8+ double-positive T cells.

Japanese encephalitis virus persists in the human reproductive epithelium and porcine reproductive tissues

“…As previously demonstrated in young piglets [8,50], adult pigs also had JEV persistence in tonsils, lymph nodes, brain, and nasal mucosa collected 28 days after inoculation (S8 Fig).…”

A case report of Japanese encephalitis in Paracelis, Mountain Province, the Philippines

“…However, the presence of a pig inside the case’s residence strengthened the evidence for the diagnosis of JE, as pigs are its natural amplifying host, while mosquitoes are the vectors to both animals and humans, who are dead-end hosts for JEV. ( 10 )…”

Regulatory effect of Pseudomonas aeruginosa mannose-sensitive hemagglutinin on inflammation and immune function in percutaneous nephrolithotomy patients with upper urinary tract calculi complicated with infection

“…In response to Mycobacterium tuberculosis infection, peripheral CD4+CD8+DPT cells have both pro-inflammatory and anti-inflammatory effects, expressing more cytolytic markers (CD107a, granzyme B, and perforin), Th1 type cytokines (TNF, IL-2, IFN- γ), Th17 type cytokines, IL-10 ( 59 ). It has been found that peripheral CD4+CD8+DPT cells are likely to play a role in protective immunity in animals ( 60 – 62 ). In addition, peripheral CD4+CD8+DPT cells express immune memory markers, which can produce rapid Th1 response and cytotoxic response to previously infected or highly replicated persistent infected viruses, antigens, and vaccines ( 58 , 63 ).…”