Biology subjects

Patel, A. R.

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

3 recordsLinked to original sources

bioRxiv2022

Polyfunctional IL-17A+ MAIT cells are expanded in the peripheral blood of patients with HLA-B27+ axial spondyloarthritis

ObjectivesStudies in axial spondyloarthritis (axSpA) have yielded conflicting results regarding the identity of the major IL-17A-producing lymphocyte populations. The goal of this study was to comprehensively assess the production of IL-17A and related cytokines by peripheral blood lymphocytes in axSpA. MethodsPeripheral blood mononuclear cells were isolated from patients with axSpA and healthy controls matched for age, sex and HLA-B27 status. Unstimulated cells and cells activated with PMA/Ionomycin were analyzed by 25-parameter fluorescent flow cytometry. Data were analyzed by hierarchical gating, UMAP and SPICE. ResultsExcept for a reduced frequency of mucosal-associated invariant T (MAIT) cells and natural killer (NK) cells, there were no other significant differences in abundance of major lymphocyte populations in axSpA patients compared with controls. Increased IL-17A production in axSpA was observed in total non-B lymphocytes and in MAIT cells. The fraction of MAIT cells expressing the tissue residency markers CD69 and CD103 was increased in axSpA. CD103 positive MAIT cells were enriched for IL-17A producers. axSpA patients demonstrated an expansion of MAIT cell subsets producing IL-17A, IL-17F, GM-CSF and TNF. This expansion was only observed in HLA-B27+ patients. ConclusionsWe document an expansion of polyfunctional IL-17A+ MAIT cells in the peripheral blood of HLA-B27+ patients with axSpA. These results are consistent with the implied role of intestinal dysbiosis or inflammation in axSpA pathogenesis. Key messagesWhat is already known about this subject? O_LIVarious IL-17A-producing lymphocyte populations have been implicated in the pathogenesis of axSpA. C_LI What does this study add? O_LIPolyfunctional MAIT cells capable of producing IL-17A, IL-17F, GM-CSF and TNF are expanded in the peripheral blood of HLA-B27+ patients with axSpA. C_LI How might this impact on clinical practice or future developments? O_LIOverproduction of IL-17A by MAIT cells is the most consistent finding of peripheral blood lymphocyte studies in axSpA. C_LIO_LIOur data support the pathogenetic link between intestinal and axial inflammation in axSpA. C_LI

immunology↗

bioRxiv2021

Infectivity of three Mayaro Virus (Genus Alphavirus, Family Togaviridae) geographic isolates in human cell lines

Mayaro virus (MAYV) is an emergent arthropod-borne virus that causes an acute febrile illness accompanied by arthralgia, similar to chikungunya virus. Increasing urbanization of MAYV outbreaks in the Americas has led to concerns that this virus could further expand its geographic range. Given the potential importance of this pathogen, we sought to fill some critical gaps in knowledge regarding MAYV infectivity and geographic variation. This study describes the cytopathogenicity of MAYV in human dermal fibroblasts, human skeletal muscle satellite cells, human embryonic kidney cells (HEK), peripherally derived human macrophages, and Vero cells. MAYV strain isolated from Bolivia (MAYV-U) infected cells more rapidly compared to MAYV strains isolated in Peru and Brazil (MAYV-P; MAYV-B), with high titers (1x108 pfu/ml) peaking at 37 hours post infection. MAYV-U also caused the most cytopathic effect in a time dependent manner. Furthermore, differently from the other two prototypic strains, MAYV-U harbors unique mutations in the E2 protein, D60G and S205F, likely to interact with the host cell receptor, which may explain the observed differences in infectivity. We further demonstrate that pre-treatment of cells with interferon-{beta} inhibited viral replication in a dose-dependent manner. Together, these findings advance our understanding of MAYV infection of human target cells and provide initial data regarding MAYV phenotypic variation according to geography. Author SummaryArthropod-borne viruses are of great public health concern, causing epidemics worldwide due to climate change, changes in land use, rapid urbanization, and the expanding geographic ranges of suitable vectors. Among these viruses, Mayaro is an emerging virus for which little is currently known. This study aims to answer fundamental questions of Mayaro virus biology using three geographically distinct viral strains to examine variability in infection kinetics and infectivity in susceptible cell types. We found one geographic isolate to have accelerated infection kinetics and increased cell damage because of infection. To better understand what was unique about this isolate, we compared their envelope protein, which is critical for entry into a cell. We found that the isolate with increased replication kinetics possessed mutations at sites that may promote viral entry, which could explain these findings. Together, these findings further our understanding of Mayaro virus biology and provide insight into factors that contribute to Mayaro transmission and infectivity.

microbiology↗

bioRxiv2021

Zoonotic potential of a novel bat morbillivirus

Morbilliviruses are amongst the most contagious viral pathogens that infect mammals. Metagenomic surveys have identified numerous morbillivirus sequences in bats, but no full-length authentic morbillivirus has been isolated or characterized from bats. Here we detail the discovery of full-length Myotis Bat Morbillivirus (MBaMV) from a bat surveillance program in Brazil. After determining that MBaMV utilizes bat CD150 but not human CD150 as an entry receptor, we generated an infectious clone of MBaMV using reverse genetics. MBaMV exhibited features consistent with other morbilliviruses, including pleomorphic virions, P-editing and the rule-of-six. MBaMV replicated well in human epithelial cell lines in a nectin-4 dependent manner. Surprisingly, MBaMV was able to infect human macrophages in a CD150-independent manner. However, MBaMV was restricted by cross-neutralizing human sera and did not evade the human innate immune system, indicating that while zoonotic spillover into humans may be possible, MBaMV replication in humans would likely be restricted.

microbiology↗