Biology subjects

Jimenez, A. R.

Publications and source records attributed to Jimenez, A. R..

3 recordsLinked to original sources

bioRxiv2024

Chikungunya Virus Release is Reduced by TIM-1 Receptors Through Binding of Envelope Phosphatidylserine

T-cell immunoglobin and mucin domain protein-1 (TIM-1) mediates entry of Chikungunya virus (CHIKV) into some mammalian cells through the interaction with envelope phospholipids. While this interaction enhances entry, TIM has been shown to tether newly formed HIV and Ebola virus particles, limiting their efficient release. In this study, we investigate the ability of surface receptors such as TIM-1 to sequester newly budded virions on the surface of infected cells. We established a luminescence reporter system to produce Chikungunya viral particles that integrate nano-luciferase and easily quantify viral particles. We found that TIM-1 on the surface of host cells significantly reduced CHIKV release efficiency in comparison to other entry factors. Removal of cell surface TIM-1 through direct cellular knock-out or altering the cellular lipid distribution enhanced CHIKV release. Over the course of infection, CHIKV was able to counteract the tethering effect by gradually decreasing the surface levels of TIM-1 in a process that appears to be mediated by the nonstructural protein 2. This study highlights the importance of phosphatidylserine receptors in mediating not only the entry of CHIKV but also its release and could aid in developing cell lines capable of enhanced vaccine production. ImportanceChikungunya virus (CHIKV) is an enveloped alphavirus transmitted by the bites of infectious mosquitoes. Infection with CHIKV results in the development of fever, joint pain, and arthralgia that can become chronic and last for months after infection. Prevention of this disease is still highly focused on vector control strategies. In December 2023, a new live attenuated vaccine against CHIKV was approved by the FDA. We aimed to study the cellular factors involved in CHIKV egress, to better understand CHIKVs ability to efficiently infect and spread among a wide variety of cell lines. We found that TIM-1 receptors can significantly abrogate CHIKVs ability to efficiently exit infected cells. This information can be beneficial for maximizing viral particle production in laboratory settings and during vaccine manufacturing.

microbiology↗

bioRxiv2022

Phosphatidylserine within the Viral Membrane Enhances Chikungunya Virus Infectivity in a Cell-type Dependent Manner

Chikungunya virus (CHIKV), an alphavirus of the Togaviridae family, is the causative agent of the human disease chikungunya fever (CHIKF), which is characterized by debilitating acute and chronic arthralgia. No licensed vaccines or antivirals exist for CHIKV. Preventing the attachment of viral particles to host cells is an attractive intervention strategy. Viral entry of enveloped viruses from diverse families including Filoviridae and Flaviviridae is mediated or enhanced by phosphatidylserine receptors (PSRs). PSRs facilitate the attachment of enveloped viruses to cells by binding to exposed phosphatidylserine (PS) in the viral lipid membrane - a process termed viral apoptotic mimicry. To investigate the role of viral apoptotic mimicry during CHIKV infection, we produced viral particles with discrete amounts of exposed PS on the virion envelope by exploiting the cellular distribution of phospholipids at the plasma membrane. We found that CHIKV particles containing high outer leaflet PS (produced in cells lacking flippase activity) were more infectious in Vero cells than particles containing low levels of outer leaflet PS (produced in cells lacking scramblase activity). However, the same viral particles were similarly infectious in NIH3T3 and HAP1 cells, suggesting PS levels can influence infectivity only in cells with high levels of PSRs. Interestingly, PS-dependent CHIKV entry was observed in mosquito Aag2 cells, but not C6/36 cells. These data demonstrate that CHIKV entry via viral apoptotic mimicry is cell-type dependent. Furthermore, viral apoptotic mimicry has a mechanistic basis to influence viral dynamics in vivo in both the human and mosquito host. ImportanceOutbreaks of Chikungunya virus (CHIKV) have occurred throughout Africa, Asia, and Europe. Climate change permits the expansion of Aedes mosquito vectors into more temperate regions, broadening the geographic range and increasing the frequency of future human outbreaks. The molecular basis underlying the broad host and cellular tropism of CHIKV remains unresolved. While several host molecules have been implicated in CHIKV viral attachment and entry, the role of lipid-mediated attachment (viral apoptotic mimicry) is unclear. We observed that higher levels of externalized phosphatidylserine (PS) in the viral lipid bilayer correlated with enhanced CHIKV infectivity in mammalian cells abundant with PS receptors and lacking alternative attachment factors. Interestingly, CHIKV infection in mosquito Aag2 cells was also affected by viral PS accessibility. This study further delineates the role of virus-cell attachment molecules in CHIKV infection. Viral apoptotic mimicry has potential to influence CHIKV dynamics in vivo in both the human and mosquito host.

microbiology↗

bioRxiv2020

The effects of Hurricane Otto on the soil ecosystems of three forest types in the Northern Zone of Costa Rica

Hurricanes rapidly deposit large amounts of canopy material onto tropical forest floors, stimulating metabolic processes involved in the decomposition of these materials and production of N and C resources into the food web. However, little is known about the effects that hurricanes have on specific soil microbial taxa or functional groups involved in these processes. The objectives of this study were to determine how Hurricane Otto influenced three different tropical forest soil ecosystems within the first 8 months after causing damage to a tropical forest by assessing the soil C and N factors and how the soil bacterial and fungal community compositions differed before and after the hurricane. Soil samples were collected from five 2000 m2 permanent plots in Lowland, Upland and Riparian forest systems within the same area in the Northern Zone of Costa Rica. Standard methods were used to measure the amounts Total N, NO3-, NH4+, Total organic C, and Biomass C, while Illumina MiSeq methods were used to generate bacterial and fungal sequences. All data were analyzed using univariate and multivariate statistical methods. Using this "before and after" study design, it was found that the levels of the inorganic N and Biomass C were greater in the Post-Hurricane soil samples. The mean proportion of DNA sequences of complex C degrading/lignin degrading, NH4+-producing, and ammonium oxidizing bacteria, and the complex C degrading/wood rot/lignin degrading and ectomycorrhizal fungi also were greater in the Post-Hurricane soils. We also provide evidence that the excessive amounts of canopy leaf litter and woody debris deposited on the forest floor during Hurricane Otto appears to be selecting for genera that become more dominant Post-Hurricane, perhaps because they may be better able to rapidly process the newly deposited C and N-rich canopy material. This is a rare "before and after" a natural hurricane design that warrants further monitoring.

microbiology↗