Human TRIM5α potently restricts particular strains of murine leukemia viruses (the so-called N-tropic strains) but not others (the B- or NB-tropic strains) during early stages of infection. We show that overexpression of SUMO-1 in human 293T cells, but not in mouse MDTF cells, profoundly blocks N-MLV infection. This block is dependent on the tropism of the incoming virus, as neither B-, NB-, nor the mutant R110E of N-MLV CA (a B-tropic switch) are affected by SUMO-1 overexpression. The block occurred prior to reverse transcription and could be abrogated by large amounts of restricted virus. Knockdown of TRIM5α in 293T SUMO-1-overexpressing cells resulted in ablation of the SUMO-1 antiviral effects, and this loss of restriction could be restored by expression of a human TRIM5α shRNA-resistant plasmid. Amino acid sequence analysis of human TRIM5α revealed a consensus SUMO conjugation site at the N-terminus and three putative SUMO interacting motifs (SIMs) in the B30.2 domain. Mutations of the TRIM5α consensus SUMO conjugation site did not affect the antiviral activity of TRIM5α in any of the cell types tested. Mutation of the SIM consensus sequences, however, abolished TRIM5α antiviral activity against N-MLV. Mutation of lysines at a potential site of SUMOylation in the CA region of the Gag gene reduced the SUMO-1 block and the TRIM5α restriction of N-MLV. Our data suggest a novel aspect of TRIM5α-mediated restriction, in which the presence of intact SIMs in TRIM5α, and also the SUMO conjugation of CA, are required for restriction. We propose that at least a portion of the antiviral activity of TRIM5α is mediated through the binding of its SIMs to SUMO-conjugated CA.
Along with the motor symptoms, Parkinson’s disease (PD) patients experience a wide range of non-motor problems including visual disturbances. These are multifaceted, but often underreported as such. In a visual survey questionnaire, 78% PD patients reported at least one problem related to vision or visuospatial functioning. The most frequent encountered problems are impaired contrast sensitivity, color discrimination, visuospatial processing, ocular or eyelid movements and diplopia followed by visual misperceptions and hallucinations. Some patients report dry eyes, ocular pain or photophobia. The pathophysiological basis of the visual disturbances is not completely understood. Changes in the visual cortex were detected with functional MRI before the visual symptoms were clinically evident. Further studies are necessary to determine how these changes will contribute to development of visual symptoms in PD patients. Other authors consider a dopaminergic deficit in the retina to be responsible for some of these symptoms, being known that dopamine is the major neurotransmitter in the amacrine and interplexiform cells in the retina. Visual hallucinations are likely to be a result of disruption across related yet diverse neural circuitry. The therapy is only symptomatic and not always satisfactory. It includes ophthalmological treatment and specific treatment for hallucinations. Optical Coherence Tomography (OCT) is a new investigation method who offers quantitative morphology of gross retinal histology. The thinning of the peripapillary retinal nerve fiber layer was observed in PD. Some studies mentioned that macular thickness measured by the OCT could be a promising biomarker of PD. This work shows how complex the visual problems in PD patients can be and the importance of a thorough and multidisciplinary approach.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.