Innate immunity in the pathogenesis of polytropic retrovirus infection in the central nervous system

Abstract

Neuroinflammation, including astrogliosis, microgliosis, and the production of proinflammatory cytokines and chemokines is a common response in the central nervous system (CNS) to virus infection, including retrovirus infection. However, the contribution of this innate immune response in disease pathogenesis remains unresolved. Analysis of the neuroinflammatory response to polytropic retrovirus infection in the mouse has provided insight into the potential contribution of the innate immune response to retrovirus-induced neurologic disease. In this model, retroviral pathogenesis correlates with the induction of neuroinflammatory responses including the activation of astrocytes and microglia, as well as the production of proinflammatory cytokines and chemokines. Studies of the neuroviru-lent determinants of the polytropic envelope protein as well as studies with knockout mice suggest that retroviral pathogenesis in the brain is multifaceted and that cytokine and chemokine production may be only one mechanism of disease pathogenesis. Analysis of the activation of the innate immune response to retrovirus infection in the CNS indicates that toll-like receptor 7 (TLR7) is a contributing factor to retrovirus-induced neuroinflammation, but that other factors can compensate for the lack of TLR7 in inducing both neuroinflammation and neurologic disease.

Macrophage Delivery of Nanoformulated Antiretroviral Drug to the Brain in a Murine Model of NeuroAIDS

“…In Figure 2 it was demonstrated that BMM migration occurs readily toward neuroinflammatory sites. In murine HIVE, the association between such cell migration and neuroinflammation involves activation of astrocytes and microglia and consequent pro-inflammatory CNS responses (31–36). In order to determine whether BMM carrying ART can migrate into HIVE affected brain regions we determined NP levels in brain 3 days following intravenous injection of rDHPE-IDV-NP-BMM.…”

The cell biology of Chikungunya virus infection

“…On one hand, mechanisms that favour non‐cytolytic viral clearance may preserve postmitotic neurones that could not be replenished or neuronal connections that could not be re‐established may promote latent viral infection. On the other, there is a danger that an associated pro‐inflammatory response would have undesirable consequences of neuroinflammation that has been seen for other viruses (Peterson and Du, ), even for those that are not obviously encephalitogenic (Jurgens et al ., ). As the human brain has a particularly lengthy period of postnatal development (Johnson, ), any sort of neuroinflammatory damage to neonatal brain regions could affect cognitive and psychological functions later in life (Cohly and Panja, ; Hagberg and Mallard, ).…”

Toll-like receptors in inflammation of the central nervous system

“…Studies with mouse model of polytropic retrovirus infection, neurovirulent determinants of the polytropic envelope protein and TLR7 KO mice suggest that retroviral pathogenesis in the brain is multifaceted and that cytokine and chemokine production may be only one mechanism involved. TLR7 is a contributing factor to retrovirus-induced neuroinflammation, but other factors can compensate for the lack of TLR7 in inducing both neuroinflammation and neurologic disease [70,71].…”