Diverse viral glycoproteins as well as CD4 co-package into the same human immunodeficiency virus (HIV-1) particles

Devon A Gregory,Tiffany M Lucas,Marc C Johnson,Grace Y Olinger

doi:10.1186/1742-4690-11-28

Devon A Gregory, Tiffany M Lucas + Show 2 more

Open Access

https://doi.org/10.1186/1742-4690-11-28

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Abstract

BackgroundRetroviruses can acquire not only their own glycoproteins as they bud from the cellular membrane, but also some cellular and foreign viral glycoproteins. Many of these non-native glycoproteins are actively recruited to budding virions, particularly other viral glycoproteins. This observation suggests that there may be a conserved mechanism underlying the recruitment of glycoproteins into viruses. If a conserved mechanism is used, diverse glycoproteins should localize to a single budding retroviral particle. On the other hand, if viral glycoproteins have divergent mechanisms for recruitment, the different glycoproteins could segregate into different particles.ResultsTo determine if co-packaging occurs among different glycoproteins, we designed an assay that combines virion antibody capture and a determination of infectivity based on a luciferase reporter. Virions were bound to a plate with an antibody against one glycoprotein, and then the infectivity was measured with cells that allow entry only with a second glycoprotein. We tested pairings of glycoproteins from HIV, murine leukemia virus (MLV), Rous sarcoma virus (RSV), vesicular stomatitis virus (VSV), and Ebola virus. The results showed that glycoproteins that were actively recruited into virions were co-packaged efficiently with each other. We also tested cellular proteins and found CD4 also had a similar correlation between active recruitment and efficient co-packaging, but other cellular proteins did not.ConclusionGlycoproteins that are actively incorporated into HIV-1 virions are efficiently co-packaged into the same virus particles, suggesting that the same general mechanism for recruitment may act in many viruses.

Highlights

Retroviruses can acquire their own glycoproteins as they bud from the cellular membrane, and some cellular and foreign viral glycoproteins
Visualization of glycoprotein recruitment by SEM We have previously shown that the distribution of glycoproteins relative to viral assembly sites can be imaged by scanning electron microscopy (SEM) [4]
murine leukemia virus (MLV) Env and Vesicular stomatitis virus glycoprotein (VSV-G) are two glycoproteins that efficiently form infectious pseudotyped particles with Human immunodeficiency virus (HIV-1) and that appear highly enriched at HIV-1 assembly sites by SEM

Summary

Introduction

Retroviruses can acquire their own glycoproteins as they bud from the cellular membrane, and some cellular and foreign viral glycoproteins Many of these non-native glycoproteins are actively recruited to budding virions, other viral glycoproteins. This observation suggests that there may be a conserved mechanism underlying the recruitment of glycoproteins into viruses. With some retrovirus and glycoprotein pseudotype combinations, incorporation appears to be an active process [4] This observation raises questions about whether many enveloped viruses share a basic conserved mechanism for acquiring viral glycoproteins during assembly and what such a mechanism might be. It is unlikely that a direct physical interaction between viral glycoproteins and Gag is the primary mechanism of active pseudotyping

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