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
- 1Department of Chemical Engineering, Howard University, Washington, District of Columbia, United States of America
- 2Center for Sickle Cell Disease, Howard University, Washington, District of Columbia, United States of America
Abstract
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 Ca2+ and pH levels were below 2 mM and 7.4, respectively, (b) a dispersed state when serum to virus ratio was high, but Ca2+ and pH levels were still below 2mM and 7.4, respectively, and (c) a Ca-induced aggregated state when Ca2+ 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, Ca2+, 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.
Related
- IgM monoclonal antibodies reduce IgG-mediated antibody-dependent enhancement of Zika and dengue virus infectivity
- Additional blood meals increase mosquito infectivity by accelerating the transcriptional development of Plasmodium sporozoites
- Stochastic epidemic models with pulse vaccination, varying infectivity and waning immunity
- The specific interface for selenocysteine-decoding tRNA in HIV-1 Gag MAdomain regulates progeny virion infectivity
- Intraspecific variation at the free-living stage of a soil-borne pathogen is organized into an exploration syndrome associated with infectivity
BibTeX
@article{chang2026hiv1,
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}},
author = {Tzu-Lan Chang and Ayobami I. Ogundiran and Andrey Ivanov and Gabrielle Torain and Sergei Nekhai and Preethi L. Chandran},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0357567},
url = {https://doi.org/10.1371/journal.pone.0357567},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Tzu-Lan Chang
AU - Ayobami I. Ogundiran
AU - Andrey Ivanov
AU - Gabrielle Torain
AU - Sergei Nekhai
AU - Preethi L. Chandran
PY - 2026
DA - 2026/09/09
JO - PLOS One
DO - 10.1371/journal.pone.0357567
UR - https://doi.org/10.1371/journal.pone.0357567
AB - 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 Ca2+ and pH levels were below 2 mM and 7.4, respectively, (b) a dispersed state when serum to virus ratio was high, but Ca2+ and pH levels were still below 2mM and 7.4, respectively, and (c) a Ca-induced aggregated state when Ca2+ 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, Ca2+, 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.
SN - 1932-6203
ER -