Protective and Pathogenic Responses to Chikungunya Virus Infection

Abstract

Chikungunya virus (CHIKV) is an arbovirus responsible for causing epidemic outbreaks of human disease characterized by painful and often debilitating arthralgia. Recently CHIKV has moved into the Caribbean and the Americas resulting in massive outbreaks in naïve human populations. Given the importance of CHIKV as an emerging disease, a significant amount of effort has gone into interpreting the virus-host interactions that contribute to protection or virus-induced pathology following CHIKV infection, with the long term goal of using this information to develop new therapies or safe and effective anti-CHIKV vaccines. This work has made it clear that numerous distinct host responses are involved in the response to CHIKV infection, where some aspects of the host innate and adaptive immune response protect from or limit virus-induced disease, while other pathways actually exacerbate the virus-induced disease process. This review will discuss mechanisms that have been identified as playing a role in the host response to CHIKV infection and illustrate the importance of carefully evaluating these responses to determine whether they play a protective or pathologic role during CHIKV infection.

Atypical Clinical Presentations of Acute Phase Chikungunya Virus Infection in Older Adults

“…In older adults, two phenomena could result in poor efficiency of the immune response in CHIKV infection: lymphopenia and age‐related changes in T‐cell immunity. Experimental models have documented the capacity of CHIKV to infect fibroblasts of the connective tissue, which activates the innate immune system with production of type 1 interferon (INF) . Higher levels of type 1 INF induce cell death in lymphocytes .…”

“…The onset of the adaptive response through activation and proliferation of CD8 + T‐cells occurs in the early stage of the infection . CD4 + T‐cells mediate the adaptive response later—after infection . Aging is characterized by a reduction in naïve T‐cells and accumulation of immunosenescent T‐cells that have exhausted their functional capacity.…”

Chikungunya virus: epidemiology, replication, disease mechanisms, and prospective intervention strategies

“…142). Activated macrophages are the primary infiltrating cell in infected tissues (Figure 3 and refs.…”

Cutaneous features of Zika virus infection: a clinicopathological overview

“…Human keratinocytes are permissive to ZIKV replication, as suggested by the cytopathic effects observed in experimentally infected cells . In addition, apoptotic blebs serve as shelter for the virus, allowing it to evade the host's cellular and humoral immune response …”