{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T18:09:13Z","timestamp":1788977353336,"version":"build-2803163510"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NSF","award":["2000175"],"award-info":[{"award-number":["2000175"]}]},{"name":"NSF","award":["2000175"],"award-info":[{"award-number":["2000175"]}]},{"name":"NIH","award":["R03AI167762"],"award-info":[{"award-number":["R03AI167762"]}]},{"name":"NIH","award":["1R01HL125005"],"award-info":[{"award-number":["1R01HL125005"]}]},{"name":"NIH","award":["5U54MD007597"],"award-info":[{"award-number":["5U54MD007597"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    The goal of the study is to determine if the N-glycosylation on a virus affects its diffusion or solution state in different environmental conditions, and if the nature of the solution states has any consequence for the virus infectivity. HIV-1 lentivirus is frequently pseudo-typed with the envelope protein of Vesicular Stomatitis Virus, VSV-G, for gene and cell therapy applications. VSV-G proteins have complex type N-glycans. The diffusion profile of the lentivirus having VSV-G envelope proteins was monitored in different solution conditions using Dynamic Light Scattering, and inferences checked by AFM, filtration, antibody, and p24 ELISA experiments. The virus switched between one of three solution states in response to changes in its environment: (a) a self-aggregated state when serum to virus ratio was low, and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and pH levels were below 2 mM and 7.4, respectively, (b) a dispersed state when serum to virus ratio was high, but Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and pH levels were still below 2mM and 7.4, respectively, and (c) a Ca-induced aggregated state when Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and pH levels exceeded 2mM and 7.4 respectively. The diffusion peak of the aggregated virus can be pulled out by antibodies against VSV-G or can be filtered out with attendant loss in p24 count and infectivity. The three solution states exhibited significantly different infectivity levels. Interestingly, the trigger conditions for switching the virus solution state occur at physiological levels of pH, Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , and serum, implying that small deviations from the homeostatic conditions can induce large changes in virus infectivity. The ability to exist and switch between three solution states was lost when the terminal sialic acid and galactose residues on the virus envelope protein were cleaved. It appears that the complex N-glycans on a virus allow the latter to respond to deviations from homeostatic environmental conditions by switching solution states.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0357567","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T17:38:55Z","timestamp":1788975535000},"page":"e0357567","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["HIV-1 lentivirus with VSV-G envelope: Complex N glycosylation governs shifts in aggregation and infectivity state at close to physiological pH, serum, and Ca2+ levels"],"prefix":"10.1371","volume":"21","author":[{"given":"Tzu-Lan","family":"Chang","sequence":"first","affiliation":[{"name":"Howard University","place":["Washington, District of Columbia, United States of America"],"department":["Department of Chemical Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayobami I.","family":"Ogundiran","sequence":"additional","affiliation":[{"name":"Howard University","place":["Washington, District of Columbia, United States of America"],"department":["Department of Chemical Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey","family":"Ivanov","sequence":"additional","affiliation":[{"name":"Center for Sickle Cell Disease, Howard University","place":["Washington, District of Columbia, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"Torain","sequence":"additional","affiliation":[{"name":"Howard University","place":["Washington, District of Columbia, United States of America"],"department":["Department of Chemical Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei","family":"Nekhai","sequence":"additional","affiliation":[{"name":"Center for Sickle Cell Disease, Howard University","place":["Washington, District of Columbia, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0624-671X","authenticated-orcid":true,"given":"Preethi L.","family":"Chandran","sequence":"additional","affiliation":[{"name":"Howard University","place":["Washington, District of Columbia, United States of America"],"department":["Department of Chemical Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"issue":"1","key":"pone.0357567.ref001","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1007\/BF02411415","article-title":"The role of high-mannose and complex asparagine-linked glycans in the secretion and stability of glycoproteins","volume":"180","author":"A Driouich","year":"1989","journal-title":"Planta"},{"issue":"19","key":"pone.0357567.ref002","doi-asserted-by":"crossref","first-page":"13914","DOI":"10.1016\/S0021-9258(19)85189-X","article-title":"Structures of the complex glycans found on the beta-subunit of (Na,K)-ATPase","volume":"268","author":"MJ Treuheit","year":"1993","journal-title":"J Biol Chem"},{"issue":"5","key":"pone.0357567.ref003","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.tim.2007.03.003","article-title":"Virus glycosylation: role in virulence and immune interactions","volume":"15","author":"DJ Vigerust","year":"2007","journal-title":"Trends Microbiol"},{"key":"pone.0357567.ref004","doi-asserted-by":"crossref","unstructured":"Shrimal S, Cherepanova NA, Gilmore R. 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A new class of mutant defective in glycosylation and transport of G protein","volume":"261","author":"GJ Kotwal","year":"1986","journal-title":"J Biol Chem"},{"issue":"19","key":"pone.0357567.ref010","doi-asserted-by":"crossref","first-page":"8936","DOI":"10.1016\/S0021-9258(19)84472-1","article-title":"Role of glycosylation in transport of vesicular stomatitis virus envelope glycoprotein. 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Cing\u00f6z","year":"2019","journal-title":"mBio"},{"issue":"8","key":"pone.0357567.ref017","doi-asserted-by":"crossref","first-page":"5871","DOI":"10.1128\/jvi.71.8.5871-5877.1997","article-title":"Pseudotyping human immunodeficiency virus type 1 (HIV-1) by the glycoprotein of vesicular stomatitis virus targets HIV-1 entry to an endocytic pathway and suppresses both the requirement for Nef and the sensitivity to cyclosporin A","volume":"71","author":"C Aiken","year":"1997","journal-title":"J Virol"},{"issue":"2","key":"pone.0357567.ref018","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1006\/viro.1995.1016","article-title":"Vpr is required for efficient replication of human immunodeficiency virus type-1 in mononuclear phagocytes","volume":"206","author":"RI Connor","year":"1995","journal-title":"Virology"},{"issue":"11","key":"pone.0357567.ref019","doi-asserted-by":"crossref","first-page":"6705","DOI":"10.1128\/jvi.69.11.6705-6711.1995","article-title":"Human 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curves in Dynamic Light Scattering","volume":"5","author":"PL Chandran","year":"2020","journal-title":"MRS Advances"},{"issue":"12","key":"pone.0357567.ref023","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1080\/01932691.2011.625523","article-title":"Dynamic Light Scattering Based Microelectrophoresis: Main Prospects and Limitations","volume":"33","author":"V Uskokovi\u0107","year":"2012","journal-title":"J Dispers Sci Technol"},{"issue":"2","key":"pone.0357567.ref024","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/BF02723037","article-title":"Aggregated proteins in serum","volume":"32","author":"J Prachar","year":"1996","journal-title":"In Vitro Cell Dev Biol Anim"},{"issue":"22","key":"pone.0357567.ref025","doi-asserted-by":"crossref","first-page":"13396","DOI":"10.1128\/JVI.01962-14","article-title":"Characterization of pH-sensitive molecular switches that trigger the structural transition of vesicular stomatitis virus glycoprotein from the postfusion state toward the prefusion state","volume":"88","author":"A Ferlin","year":"2014","journal-title":"J Virol"},{"issue":"7","key":"pone.0357567.ref026","doi-asserted-by":"crossref","first-page":"108042","DOI":"10.1016\/j.celrep.2020.108042","article-title":"Identification of a pH-Sensitive Switch in VSV-G and a Crystal Structure of the G Pre-fusion State Highlight the VSV-G Structural Transition Pathway","volume":"32","author":"F Beilstein","year":"2020","journal-title":"Cell Rep"},{"issue":"22","key":"pone.0357567.ref027","doi-asserted-by":"crossref","first-page":"13396","DOI":"10.1128\/JVI.01962-14","article-title":"Characterization of pH-sensitive molecular switches that trigger the structural transition of vesicular stomatitis virus glycoprotein from the postfusion state toward the prefusion state","volume":"88","author":"A Ferlin","year":"2014","journal-title":"J Virol"},{"issue":"1","key":"pone.0357567.ref028","article-title":"Mechanism of membrane fusion induced by vesicular stomatitis virus G protein","volume":"114","author":"IS Kim","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0357567.ref029","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1021\/bp060121o","article-title":"Proteomic analysis for the assessment of different lots of fetal bovine serum as a raw material for cell culture. Part IV. Application of proteomics to the manufacture of biological drugs","volume":"22","author":"X Zheng","year":"2006","journal-title":"Biotechnology Progress"},{"issue":"1","key":"pone.0357567.ref030","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/71740","article-title":"Learning from lentiviruses","volume":"24","author":"M Emerman","year":"2000","journal-title":"Nat Genet"},{"key":"pone.0357567.ref031","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.omtm.2021.03.018","article-title":"HIV-based lentiviral vectors: origin and sequence differences","volume":"21","author":"NM Johnson","year":"2021","journal-title":"Mol Ther Methods Clin Dev"},{"key":"pone.0357567.ref032","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.molmed.2004.03.003","article-title":"Vesicular stomatitis virus: re-inventing the bullet","volume":"10","author":"BD Lichty","year":"2004","journal-title":"Trends in Molecular Medicine"},{"issue":"22","key":"pone.0357567.ref033","doi-asserted-by":"crossref","first-page":"12236","DOI":"10.1128\/JVI.78.22.12236-12242.2004","article-title":"Vesicular stomatitis virus evolution during alternation between persistent infection in insect cells and acute infection in mammalian cells is dominated by the persistence phase","volume":"78","author":"S Z\u00e1rate","year":"2004","journal-title":"J Virol"},{"issue":"18","key":"pone.0357567.ref034","doi-asserted-by":"crossref","first-page":"7306","DOI":"10.1073\/pnas.1214441110","article-title":"LDL receptor and its family members serve as the cellular receptors for vesicular stomatitis virus","volume":"110","author":"D Finkelshtein","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pone.0357567.ref035","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1038\/s41467-018-03432-4","article-title":"Structural basis for the recognition of LDL-receptor family members by VSV glycoprotein","volume":"9","author":"J Nikolic","year":"2018","journal-title":"Nat Commun"},{"key":"pone.0357567.ref036","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/s41434-020-00193-y","article-title":"The stability of envelope-pseudotyped lentiviral vectors","volume":"28","author":"IJC Dautzenberg","year":"2021","journal-title":"Gene Ther"},{"issue":"23","key":"pone.0357567.ref037","doi-asserted-by":"crossref","first-page":"11747","DOI":"10.1128\/JVI.75.23.11747-11754.2001","article-title":"Vesicular stomatitis virus G-pseudotyped lentivirus vectors mediate efficient apical transduction of polarized quiescent primary alveolar epithelial cells","volume":"75","author":"Z Borok","year":"2001","journal-title":"J Virol"},{"issue":"5","key":"pone.0357567.ref038","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/jgm.1022","article-title":"Factors that influence VSV-G pseudotyping and transduction efficiency of lentiviral vectors-in vitro and in vivo implications","volume":"9","author":"DC Farley","year":"2007","journal-title":"J Gene Med"},{"issue":"10","key":"pone.0357567.ref039","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1002\/jgm.788","article-title":"Retinal cell type expression specificity of HIV-1-derived gene transfer vectors upon subretinal injection in the adult rat: influence of pseudotyping and promoter","volume":"7","author":"A-P Bemelmans","year":"2005","journal-title":"J Gene Med"},{"key":"pone.0357567.ref040","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.virusres.2013.06.003","article-title":"Understanding and altering cell tropism of vesicular stomatitis virus","volume":"176","author":"E Hastie","year":"2013","journal-title":"Virus Res"},{"issue":"10","key":"pone.0357567.ref041","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1080\/14712598.2020.1787981","article-title":"A tool with many applications: vesicular stomatitis virus in research and medicine","volume":"20","author":"AM Munis","year":"2020","journal-title":"Expert Opin Biol Ther"},{"issue":"37","key":"pone.0357567.ref042","doi-asserted-by":"crossref","first-page":"32840","DOI":"10.1021\/acsomega.2c03517","article-title":"Emerging Biomedical Applications of the Vesicular Stomatitis Virus Glycoprotein","volume":"7","author":"S Rehman","year":"2022","journal-title":"ACS Omega"},{"issue":"12","key":"pone.0357567.ref043","doi-asserted-by":"crossref","first-page":"9873","DOI":"10.1128\/JVI.72.12.9873-9880.1998","article-title":"Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery","volume":"72","author":"R Zufferey","year":"1998","journal-title":"J Virol"},{"key":"pone.0357567.ref044","article-title":"Production of vesicular stomatitis virus g glycoprotein (vsv-g) pseudotyped retroviral vectors","volume":"52","author":"HL Lo","year":"2007","journal-title":"Current Protocols in Human Genetics"},{"key":"pone.0357567.ref045","article-title":"Collective infection of cells by viral aggregates promotes early viral proliferation and reveals a cellular-level Allee effect","author":"I Andreu-Moreno","year":"2023","journal-title":"J Virol"},{"issue":"3","key":"pone.0357567.ref046","doi-asserted-by":"crossref","first-page":"282","DOI":"10.3390\/v12030282","article-title":"Fibrinogen gamma chain promotes aggregation of vesicular stomatitis virus in saliva","volume":"12","author":"V Anschau","year":"2020","journal-title":"Viruses"},{"key":"pone.0357567.ref047","unstructured":"Cuevas JM, Dur\u00e1n-Moreno M, Sanju\u00e1n R. Multi-virion infectious units arise from free viral particles in an enveloped virus."},{"issue":"1","key":"pone.0357567.ref048","doi-asserted-by":"crossref","DOI":"10.1093\/ve\/vez014","article-title":"Why viruses sometimes disperse in groups?\u2020","volume":"5","author":"R Sanju\u00e1n","year":"2019","journal-title":"Virus Evol"},{"key":"pone.0357567.ref049","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.02156-19","article-title":"Collective viral spread mediated by virion aggregates promotes the evolution of defective interfering particles","volume":"11","author":"I Andreu-Moreno","year":"2020","journal-title":"mBio"},{"key":"pone.0357567.ref050","doi-asserted-by":"crossref","unstructured":"DePolo NJ, Reed JD, Sheridan PL, Townsend K, Sauter SL, Jolly DJ. VSV-G pseudotyped lentiviral vector particles produced in human cells are inactivated by human serum. 2000;:218\u201322.","DOI":"10.1006\/mthe.2000.0116"},{"issue":"8","key":"pone.0357567.ref051","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1038\/gt.2013.1","article-title":"Engineering a serum-resistant and thermostable vesicular stomatitis virus G glycoprotein for pseudotyping retroviral and lentiviral vectors","volume":"20","author":"B-Y Hwang","year":"2013","journal-title":"Gene Ther"},{"issue":"10","key":"pone.0357567.ref052","doi-asserted-by":"crossref","DOI":"10.1128\/jvi.00752-23","article-title":"Shear-reversible clusters of HIV-1 in solution: stabilized by antibodies, dispersed by mucin","volume":"97","author":"AI Ogundiran","year":"2023","journal-title":"J Virol"},{"issue":"46","key":"pone.0357567.ref053","doi-asserted-by":"crossref","first-page":"13769","DOI":"10.1021\/acs.langmuir.0c01953","article-title":"Establishing Rules for Self-Adhesion and Aggregation of N-Glycan Sugars Using Virus Glycan Shields","volume":"36","author":"E Ogharandukun","year":"2020","journal-title":"Langmuir"},{"issue":"36","key":"pone.0357567.ref054","doi-asserted-by":"crossref","first-page":"9178","DOI":"10.1021\/acs.langmuir.7b01006","article-title":"Mannose Surfaces Exhibit Self-Latching, Water Structuring, and Resilience to Chaotropes: Implications for Pathogen Virulence","volume":"33","author":"HK Abeyratne-Perera","year":"2017","journal-title":"Langmuir"},{"issue":"22","key":"pone.0357567.ref055","doi-asserted-by":"crossref","first-page":"4525","DOI":"10.1039\/C9SM00579J","article-title":"Complex-type N-glycans on VSV-G pseudotyped HIV exhibit \u201ctough\u201d sialic and \u201cbrittle\u201d mannose self-adhesions","volume":"15","author":"HK Abeyratne-Perera","year":"2019","journal-title":"Soft Matter"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0357567","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T17:39:07Z","timestamp":1788975547000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0357567"}},"subtitle":[],"editor":[{"given":"Nagarajan","family":"Raju","sequence":"first","affiliation":[{"name":"Emory University","place":["UNITED STATES OF AMERICA"]}],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,9,9]]},"references-count":55,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0357567","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,9]]}}}