#plospathogens

Il team ha scoperto che la proteina Spike del nuovo virus, denominato Khosta-2, può infettare le cellule umane ed è resistente sia agli anticorpi monoclonali sia al siero di individui vaccinati per il Sars-CoV-2. Sia il Khosta-2 che il Sars-CoV2 appartengono alla stessa sottocategoria di coronavirus nota come sarbecovirus, precisano gli esperti. "La nostra ricerca dimostra ulteriormente che i sarbecovirus che circolano nella fauna selvatica al di fuori dell'Asia -anche in luoghi come la Russia occidentale, dove è stato trovato il virus Khosta-2 - rappresentano una minaccia per la salute globale e per le campagne vaccinali in corso contro il Sars-CoV-2", dichiara Michael Letko, virologo autore dello studio. La scoperta del Khosta-2 evidenzia la necessità di sviluppare vaccini universali per proteggere contro i sarbecovirus in generale, piuttosto che solo contro le varianti conosciute del SARS-CoV-2. "In questo momento ci sono gruppi che stanno cercando di trovare un vaccino che non protegga solo dalla prossima variante della SARS-2, ma che ci protegga da tutti i sarbecovirus ", spiega Letko. "Purtroppo, molti dei nostri vaccini attuali sono progettati per specifici virus che sappiamo infettare le cellule umane o per quelli che sembrano rappresentare il rischio maggiore di infettarci. Ma si tratta di un elenco in continua evoluzione. Dobbiamo ampliare la progettazione di questi vaccini per proteggere da tutti i sarbecovirus". Read the full article

Micrographs of DENV2 with different distribution of smooth and bumpy surfaced particles when incubated at different temperatures to mimic the physiological temperature in the mosquitoes (29°C, left panel), human host (37°C, middle panel) and when humans are experiencing high fever (40°C, right panel). Colour gradient from blue to red shows the rise in temperature. Xin-Ni Lim, Emerging Infectious Diseases Programme, Duke-NUS Medical School We showed some differences in their amino acid sequences and We showed some differences in their amino acid sequences and mutating these residues coupled with observing their surface structures showed which residues are important for this temperature induced structural change. Results showed that subtle mutations at different places on the envelope protein can destabilize the virus allowing them to change in structure when temperature is elevated. Due to the poor selection pressure of the artificial laboratory tissue culture system, gradual mutations of the virus is accumulated causing the virus to have bumpy surface morphology. MedicalResearch.com: What are the main findings? Response: We then look at four DENV strains that were obtained from patients (clinical isolate). In contrast to the laboratory adapted viruses, three out of four of these clinical strains maintained smooth surface morphology at 37oC. This shows that the human host selects those with smooth surface morphologies. However, when incubated at 40oC mimicking the fever temperature all virus changes to bumpy surface. MedicalResearch.com: What should readers take away from your report?  Response: For therapeutic antibody development, some antibodies have been found to be effective for smooth surface virus particles while others, bumpy surfaced. From our current studies, it informs us when to use which kind of antibodies for treatment. For example, for prevention of disease treatment where antibodies are injected to a person before they get infected with dengue, we should use those effective against the smoothed surface virus. When used in patients displaying fever symptoms, we should employ the antibodies effective against the bumpy surface particles. This study also showed that the lab adapted strain of DENV2 may not be a good model for research as their morphology is different from the clinical strains isolated from patients.  Citation: Molecular basis of dengue virus serotype 2 morphological switch from 29°C to 37°C Xin-Ni Lim ,Chao Shan ,Jan K. Marzinek ,Hongping Dong,Thiam Seng Ng,Justin S. G. Ooi,Guntur Fibriansah,Jiaqi Wang,Chandra S. Verma,Peter J. Bond ,Pei-Yong Shi ,Shee-mei Lok Published: September 19, 2019 https://doi.org/10.1371/journal.ppat.1007996 Last Modified: The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.   Read the full article

Brent Palmer Brent E. Palmer, PhD Associate Professor of Medicine Director, ClinImmune and ACI/ID Flow Cytometry Facility Division of Allergy and Clinical Immunology University of Colorado Anschutz Medical College Aurora, Colorado 80045  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Previous studies showed that in western populations, men who have sex with men (MSM) have a distinct gut microbiome composition when compared with men who have sex with women (MSW). We wanted to understand how these microbiome differences in MSM could impact their immune system. To test this, we transferred feces from healthy MSW and MSM to gnotobiotic (germ-free) mice and examined the immune system in the mice post-transplant. In mice that received transfers from MSM, there were higher frequencies of activated T cells in gut tissues, which are the primary targets of HIV. This result suggested that gut microbes associated with MSM sexual behavior may actually contribute to HIV transmission by driving activation of HIV target cells. In fact, when we stimulated human gut derived cells with gut microbes isolated from MSM and MSW, cells that were stimulated with microbes from MSM were infected at a higher rate.  MedicalResearch.com: What should readers take away from your report? Response: Our study shows that microbes associated with MSM sexual behavior can alter the immune system in a way that could increase risk for HIV infection, at least in mice. MedicalResearch.com: What recommendations do you have for future research as a result of this work? Response: These experiments were done in mice and in cell culture, so studies in human populations will be needed to demonstrate that the gut microbiome is indeed a risk factor for HIV infection. Additionally, it is still not clear how sexual behaviors specifically alter the gut microbiome - understanding how this occurs could lead to development of therapies that prevent or "reverse" these microbiome alterations. Citation: Sam X. Li, Sharon Sen, Jennifer M. Schneider, Ka-Na Xiong, Nichole M. Nusbacher, Nancy Moreno-Huizar, Michael Shaffer, Abigail J. S. Armstrong, Erin Severs, Kristine Kuhn, Charles P. Neff, Martin McCarter, Thomas Campbell, Catherine A. Lozupone, Brent E. Palmer. Gut microbiota from high-risk men who have sex with men drive immune activation in gnotobiotic mice and in vitro HIV infection. PLOS Pathogens, 2019; 15 (4): e1007611 DOI: 10.1371/journal.ppat.1007611    The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.   Read the full article