Jean K. Lim's scientific contributions

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Publications (1)

Ccr5 controls leukocytes trafficking into the CNS. Following entry and replication within the CNS, neurotropic flaviviruses, such as WNV, trigger the recruitment of CD4⁺ T cells, CD8⁺ T cells, NK cells, and peripherally derived monocytes in wild-type (Ccr5+/+) mice (a). However, in the absence of Ccr5 (Ccr5−/−), these cell subsets are unable to migrate into the CNS, eventually leading to uncontrolled virus replication and mortality. Dotted arrows represent reduced cell migration into the infected brain (b). CNS: central nervous system; WNV: West Nile virus; NK: natural killer.
Ccr5-expressing regulatory T cells mitigate CNS inflammation. After entry into the CNS, neurotropic flaviviruses such as JEV and LGTV trigger inflammation mediated by both innate immune cells and cytokines in the CNS that is mitigated by the presence of regulatory T cells (Tregs) guided into the CNS through Ccr5 expression in wild-type (Ccr5+/+) mice. Solid arrows represent the direction of Tregs into the infected site (a). In the absence of Ccr5, Treg migration into the CNS is impaired, leading to uncontrolled inflammation of the brain tissue (represented by the red shadow). Dotted arrows represent reduced migration of Tregs into the infected brain (b). CNS: central nervous system; JEV: Japanese encephalitis virus.
Optimal effector functions of NK and CD8⁺ T cells require Ccr5. NK cells and effector CD8⁺ T cells isolated from flavivirus-infected mice were tested for effective killing of target cells ex vivo and production of IFNγ and/or TNFα after ex vivo stimulation with immunodominant JEV-derived peptide or whole virus. Compared to wild-type Ccr5+/+ mice (a), NK cells and CD8⁺ cells isolated from Ccr5−/− mice were functionally impaired, leading to increased viral replication in the CNS (b). NK: natural killer; JEV: Japanese encephalitis virus; IFN: interferon; TNF: tumor necrosis factor.
CCR5 promotes persistence of flaviviruses in the brain endothelium. Neurotropic flaviviruses, including ZIKV, can infect the brain endothelium in vitro. Signaling events induced by CCL5 binding to its receptor, CCR5, lead to persistent, long-term infection of the infected endothelium (a). Blocking the CCL5:CCR5 interaction, as would be the case in CCR5Δ32 homozygosity, triggers cytopathology of the virus-infected endothelial cell that ultimately promotes viral clearance (b). ZIKV: Zika virus.
A Pocket Guide to CCR5—Neurotropic Flavivirus Edition
  • Literature Review
  • Full-text available

December 2023

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11 Reads

Viruses

Viruses

Amit Garg

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Jean K. Lim

CCR5 is among the most studied chemokine receptors due to its profound significance in human health and disease. The notion that CCR5 is a functionally redundant receptor was challenged through the demonstration of its unique protective role in the context of West Nile virus in both mice and humans. In the nearly two decades since this initial discovery, numerous studies have investigated the role of CCR5 in the context of other medically important neurotropic flaviviruses, most of which appear to support a broad neuroprotective role for this receptor, although how CCR5 exerts its protective effect has been remarkably varied. In this review, we summarize the mechanisms by which CCR5 controls neurotropic flaviviruses, as well as results from human studies evaluating a genetic link to CCR5, and propose unexplored areas of research that are needed to unveil even more exciting roles for this important receptor.

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