Unknown

Dataset Information

0

The Phosphatidylserine Receptor TIM-1 Enhances Authentic Chikungunya Virus Cell Entry.


ABSTRACT: Chikungunya virus (CHIKV) is a re-emerging, mosquito-transmitted, enveloped positive stranded RNA virus. Chikungunya fever is characterized by acute and chronic debilitating arthritis. Although multiple host factors have been shown to enhance CHIKV infection, the molecular mechanisms of cell entry and entry factors remain poorly understood. The phosphatidylserine-dependent receptors, T-cell immunoglobulin and mucin domain 1 (TIM-1) and Axl receptor tyrosine kinase (Axl), are transmembrane proteins that can serve as entry factors for enveloped viruses. Previous studies used pseudoviruses to delineate the role of TIM-1 and Axl in CHIKV entry. Conversely, here, we use the authentic CHIKV and cells ectopically expressing TIM-1 or Axl and demonstrate a role for TIM-1 in CHIKV infection. To further characterize TIM-1-dependent CHIKV infection, we generated cells expressing domain mutants of TIM-1. We show that point mutations in the phosphatidylserine binding site of TIM-1 lead to reduced cell binding, entry, and infection of CHIKV. Ectopic expression of TIM-1 renders immortalized keratinocytes permissive to CHIKV, whereas silencing of endogenously expressed TIM-1 in human hepatoma cells reduces CHIKV infection. Altogether, our findings indicate that, unlike Axl, TIM-1 readily promotes the productive entry of authentic CHIKV into target cells.

SUBMITTER: Kirui J 

PROVIDER: S-EPMC8303237 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

The Phosphatidylserine Receptor TIM-1 Enhances Authentic Chikungunya Virus Cell Entry.

Kirui Jared J   Abidine Yara Y   Lenman Annasara A   Islam Koushikul K   Gwon Yong-Dae YD   Lasswitz Lisa L   Evander Magnus M   Bally Marta M   Gerold Gisa G  

Cells 20210720 7


Chikungunya virus (CHIKV) is a re-emerging, mosquito-transmitted, enveloped positive stranded RNA virus. Chikungunya fever is characterized by acute and chronic debilitating arthritis. Although multiple host factors have been shown to enhance CHIKV infection, the molecular mechanisms of cell entry and entry factors remain poorly understood. The phosphatidylserine-dependent receptors, T-cell immunoglobulin and mucin domain 1 (TIM-1) and Axl receptor tyrosine kinase (Axl), are transmembrane protei  ...[more]

Similar Datasets

| S-EPMC3719829 | biostudies-literature
| S-EPMC3572209 | biostudies-literature
| S-EPMC10849729 | biostudies-literature
| S-EPMC4514758 | biostudies-literature
| S-EPMC4836339 | biostudies-literature
| S-EPMC4252826 | biostudies-literature
| S-EPMC4054341 | biostudies-literature
| S-EPMC6265761 | biostudies-literature
| S-EPMC6069209 | biostudies-literature
| S-EPMC5558241 | biostudies-literature