CD8+ T Cells Control Ross River Virus Infection in Musculoskeletal Tissues of Infected Mice

Abstract

Ross River virus (RRV), chikungunya virus (CHIKV), and related alphaviruses cause debilitating polyarthralgia and myalgia. Mouse models of RRV and CHIKV have demonstrated a role for the adaptive immune response in the control of these infections. However, questions remain regarding the role for T cells in viral control, including the magnitude, location, and dynamics of CD8+ T cell responses. To address these questions, we generated a recombinant RRV expressing the H-2b-restricted gp33 determinant derived from the glycoprotein (gp) of lymphocytic choriomeningitis virus (LCMV) (“RRV-LCMV”). Utilizing tetramers, we tracked gp33-specific CD8+ T cells during RRV-LCMV infection. We found that acute RRV infection induces activation of CD8+ T cell responses in lymphoid and musculoskeletal tissues that peak from 10 to 14 days post-inoculation (dpi), suggesting that CD8+ T cells contribute to control of acute RRV infection. Mice genetically deficient for CD8+ T cells or wild-type mice depleted of CD8+ T cells had elevated RRV loads in skeletal muscle tissue, but not joint-associated tissues, at 14 dpi, suggesting that the ability of CD8+ T cells to control RRV infection is tissue-dependent. Finally, adoptively transferred T cells were capable of reducing RRV loads in skeletal muscle tissue of Rag1−/− mice, indicating that T cells can contribute to the control of RRV infection in the absence of B cells and antibody. Collectively, these data demonstrate a role for T cells in the control of RRV infection and suggest that the antiviral capacity of T cells is controlled in a tissue-specific manner.

Chikungunya virus impairs draining lymph node function by inhibiting HEV-mediated lymphocyte recruitment

“…Because lymphocyte proliferation contributes to LN hypertrophy, we hypothesized that there may be a defect in lymphocyte proliferation in the dLN after pathogenic, persistent CHIKV infection. To evaluate the proliferation of bulk and CHIKV-specific T cells, we engineered recombinant CHIKV strains containing the H-2K b -restricted ovalbumin OVA 257-264 epitope (SIINFEKL) and the I-A d /I-A b -restricted OVA 323-339 epitope (ISQAVHAAHAEINEAGR) in frame with the CHIKV structural polyprotein in the 181/25 (181/25.OVA) or AF15561 (AF15561.OVA) genome (Supplemental Figure 4A), using a strategy that we previously used to evaluate T cell responses during Ross River virus infection (45). 181/25.OVA and AF15561.OVA grew similarly in BHK-21 cells (Supplemental Figure 4B).…”

Cross-protective efficacy of dendritic cells targeting conserved influenza virus antigen expressed by Lactobacillus plantarum

“…CD8 + T cell responses can provide strong protection against influenza virus infections48. Furthermore, specific CD8 + T cells result in strong pathogen-killing effects, and thus, the use of these T cells has been studied extensively5859. However, whether CD4 + T cells provide protective responses to influenza virus in mice vaccinated with recombinant L. plantarum via other mechanisms awaits further study.…”

Role of T Cells in Chikungunya Virus Infection and Utilizing Their Potential in Anti-Viral Immunity

“…However, they do not protect against CHIKV-associated pathologies as mice deficient in CD8 + T cells still developed joint inflammation (31). This observation is in contrast to other findings whereby CD8 T cells play an active role in mediating viral clearance and disease resolution in mouse models of Ross River virus (RRV) (38) and Venezuela Equine Encephalomyelitis virus (VEEV) (39). CHIKV RNA could be detected in the footpad of mice at up to 16 weeks post-challenge, suggesting that chronic CHIKV infection could persist in the footpad (40).…”