Cholesterol Depletion Inactivates XMRV and Leads to Viral Envelope Protein Release from Virions: Evidence for Role of Cholesterol in XMRV Infection

Abstract

Membrane cholesterol plays an important role in replication of HIV-1 and other retroviruses. Here, we report that the gammaretrovirus XMRV requires cholesterol and lipid rafts for infection and replication. We demonstrate that treatment of XMRV with a low concentration (10 mM) of 2-hydroxypropyl-β-cyclodextrin (2OHpβCD) partially depleted virion-associated cholesterol resulting in complete inactivation of the virus. This effect could not be reversed by adding cholesterol back to treated virions. Further analysis revealed that following cholesterol depletion, virus-associated Env protein was significantly reduced while the virions remained intact and retained core proteins. Increasing concentrations of 2OHpβCD (≥20 mM) resulted in loss of the majority of virion-associated cholesterol, causing disruption of membrane integrity and loss of internal Gag proteins and viral RNA. Depletion of cholesterol from XMRV-infected cells significantly reduced virus release, suggesting that cholesterol and intact lipid rafts are required for the budding process of XMRV. These results suggest that unlike glycoproteins of other retroviruses, the association of XMRV glycoprotein with virions is highly dependent on cholesterol and lipid rafts.

Pseudotyping of HIV-1 with Human T-Lymphotropic Virus 1 (HTLV-1) Envelope Glycoprotein during HIV-1–HTLV-1 Coinfection Facilitates Direct HIV-1 Infection of Female Genital Epithelial Cells: Implications for Sexual Transmission of HIV-1

“…HIV-1 and HTLV-1 release into supernatants of infected cells was determined either by HIV-1 p24 ELISA as described before ( 66 ) and HTLV-1 p19 ELISA (ZeptoMetrix Corporation) or by qRT-PCR measurement of viral RNA. RNA in culture supernatants from infected cells was isolated with QIAamp Viral RNA kits (Qiagen) and subjected to one-step qRT-PCR analysis with the iTaq Universal Probes One-Step kit (Bio-Rad).…”

The Lord of the NanoRings: Cyclodextrins and the battle against SARS-CoV-2

“…The use of CDs for the treatment of viral infections, trying to use their cholesterol depletion capabilities in order to inhibit the virus contagion, is becoming increasingly popular ( Baglivo et al, 2020 ). HIV and hepatitis C have been successfully treated in this way already for a long time, reaching almost complete abolishment of infectivity by HIV-1 virions ( Graham et al, 2003 , Guyader et al, 2002 , Sagan et al, 2006 , Tang et al, 2012 ). The ability of these CDs to reduce viral infectivity has also been demonstrated against human metapneumovirus (HMPV) ( Chen et al, 2019 ), herpes simplex virus 1 (HSV-1) ( Wudiri et al, 2017 , Wudiri and Nicola, 2017 ), varicella-zooster virus (VZV) ( Hambleton et al, 2007 ) and a less common one, the Newcastle disease virus (NDV) ( Cantín et al, 2007 , Martín et al, 2012 ).…”