20 research outputs found
TRPC1 participates in the HSV-1 infection process by facilitating viral entry
Mammalian transient receptor potential (TRP) channels are major components of Ca2+ signaling pathways and control a diversity of physiological functions. Here, we report a specific role for TRPC1 in the entry of herpes simplex virus type 1 (HSV-1) into cells. HSV-1-induced Ca2+ release and entry were dependent on Orai1, STIM1, and TRPC1. Inhibition of Ca2+ entry or knockdown of these proteins attenuated viral entry and infection. HSV-1 glycoprotein D interacted with the third ectodomain of TRPC1, and this interaction facilitated viral entry. Knockout of TRPC1 attenuated HSV-1-induced ocular abnormality and morbidity in vivo in TRPC1−/− mice. There was a strong correlation between HSV-1 infection and plasma membrane localization of TRPC1 in epithelial cells within oral lesions in buccal biopsies from HSV-1-infected patients. Together, our findings demonstrate a critical role for TRPC1 in HSV-1 infection and suggest the channel as a potential target for anti-HSV therapy.Fil: He, DongXu. Jiangnan University; ChinaFil: Mao, AiQin. Jiangnan University; ChinaFil: Li, YouRan. Jiangnan University; ChinaFil: Tam, SiuCheung. Chinese University Of Hong Kong; Hong KongFil: Zheng, YongTang. Kunming Institute Of Zoology Chinese Academy Of Sciences; ChinaFil: Yao, XiaoQiang. Chinese University Of Hong Kong; Hong KongFil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Ambudkar, Indu S.. National Institute Of Dental And Craniofacial Research ; Estados UnidosFil: Ma, Xin. Jiangnan University; Chin
Penicillium marneffei-Stimulated Dendritic Cells Enhance HIV-1 Trans-Infection and Promote Viral Infection by Activating Primary CD4+ T Cells
Penicillium marneffei (P. marneffei) is considered an indicator pathogen of AIDS, and the endemicity and clinical features of P. marneffei have been described. While, how the co-infection of P. marneffei exacerbate deterioration of the immune response remains poorly understood. Here we isolated P. marneffei from the cutaneous lesions of AIDS patients and analyzed its effects on HIV-1-dendritic cells (DCs) interaction. We demonstrated that the monocyte-derived dendritic cells (MDDCs) could be activated by both thermally dimorphic forms of P. marneffei for significantly promoting HIV-1 trans-infection of CD4+ T cells, while these activated MDDCs were refractory to HIV-1 infection. Mechanistically, P. marneffei-activated MDDCs endocytosed large amounts of HIV-1 and sequestrated the internalized viruses into tetrapasnin CD81+ compartments potentially for proteolysis escaping. The activated MDDCs increased expression of intercellular adhesion molecule 1 and facilitated the formation of DC-T-cell conjunctions, where much more viruses were recruited. Moreover, we found that P. marneffei-stimulated MDDCs efficiently activated resting CD4+ T cells and induced more susceptible targets for viral infection. Our findings demonstrate that DC function and its interaction with HIV-1 have been modulated by opportunistic pathogens such as P. marneffei for viral dissemination and infection amplification, highlighting the importance of understanding DC-HIV-1 interaction for viral immunopathogenesis elucidation
A Path Forming Method for Water Surface Mobile Sink Using Voronoi Diagram and Dominating Set
Experimental investigations on the shear strength and creep properties of soil-rock mixture under freeze-thaw cycles
Glutamylation of an HIV-1 protein inhibits the immune response by hijacking STING
Summary: Cyclic GMP-AMP synthase (cGAS) recognizes Y-form cDNA of human immunodeficiency virus type 1 (HIV-1) and initiates antiviral immune response through cGAS-stimulator of interferon genes (STING)-TBK1-IRF3-type I interferon (IFN-I) signalingcascade. Here, we report that the HIV-1 p6 protein suppresses HIV-1-stimulated expression of IFN-I and promotes immune evasion. Mechanistically, the glutamylated p6 at residue Glu6 inhibits the interaction between STING and tripartite motif protein 32 (TRIM32) or autocrine motility factor receptor (AMFR). This subsequently suppresses the K27- and K63-linked polyubiquitination of STING at K337, therefore inhibiting STING activation, whereas mutation of the Glu6 residue partially reverses the inhibitory effect. However, CoCl2, an agonist of cytosolic carboxypeptidases (CCPs), counteracts the glutamylation of p6 at the Glu6 residue and inhibits HIV-1 immune evasion. These findings reveal a mechanism through which an HIV-1 protein mediates immune evasion and provides a therapeutic drug candidate to treat HIV-1 infection