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[Preprint]. 2023 Dec 28:2023.12.25.573317. [Version 2] doi: 10.1101/2023.12.25.573317

Identifying Discrepancies in HIV Infectivity and Virion Maturation Using FRET-Based Detection and Quantification

Kedhar Narayan, Jeongpill Choi, Shreyas S Gujar, Aidan McGraw, Hasset Tibebe, Lilia Mei Bose, Caroline N Arnette, Taisuke Izumi
PMCID: PMC10793453  PMID: 38234844

Abstract

The maturation of HIV-1 virions is a crucial process in viral replication. Although T cells are a primary source of virus production, much of our understanding of virion maturation comes from studies using the HEK293T human embryonic kidney cell line. Notably, there is a lack of comparative analyses between T cells and HEK293T cells in terms of virion maturation efficiency in existing literature. We previously developed an advanced virion visualization system based on the FRET principle, enabling the effective distinction between immature and mature virions via fluorescence microscopy. In this study, fully infectious FRET-labeled viruses (HIV-1 Gag-iFRET) from Jurkat (a human T lymphocyte cell line) and HEK293T cells were used to assess their virion maturation rates. Our results showed that viruses originating from Jurkat cells had an infectivity rate approximately tenfold higher than that from HEK293T cells. Concerning virion maturity, HEK293T-derived virions demonstrated a maturity rate of 81.79%, consistent with other studies and our previous findings. However, virions from Jurkat cells exhibited a notably lower maturity rate of 68.67% ( p <0.0001), indicating an interesting deviation from the expected positive correlation with infectivity. These findings suggest that the initiation of virion maturation does not directly correlate with viral infectivity. Instead, these observations suggest that the rate of conical core formation following the initiation of virion maturation plays a more pivotal role in determining viral infectivity, even when the overall level of maturation is relatively low.

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