Add like
Add dislike
Add to saved papers

Both sphingomyelin and cholesterol in the host cell membrane are essential for Rubella virus entry.

Journal of Virology 2017 October 26
Rubella virus (RuV) causes a systemic infection and transplacental fetal infection causes congenital rubella syndrome. In this study, we showed that treatment of cells with sphingomyelinase inhibited RuV infection. Assays using inhibitors of serine palmitoyl transferase and ceramide transport protein demonstrated the contribution of sphingomyelin (SM) to RuV infection. Compelling evidence for direct binding of RuV to lipid membranes at neutral pH was obtained using liposome co-flotation assays. The absence of either SM or cholesterol (Chol) abrogated the RuV--liposome interaction. SM and Chol (SM/Chol) were also critical for RuV binding to erythrocytes and lymphoid cells. Removal of Ca2+ from the assay buffer or mutation of RuV envelope E1 protein Ca2+ -binding sites abrogated RuV binding to liposomes, erythrocytes, and lymphoid cells. However, RuV bound to various non-lymphoid adherent cell lines independently of extracellular Ca2+ or SM/Chol. Even in these adherent cell lines, both the E1 protein Ca2+ -binding sites and cellular SM/Chol were essential for the early stage of RuV infection, possibly affecting envelope-membrane fusion in acidic compartments. Myelin oligodendrocyte glycoprotein (MOG) has recently been identified as a cellular receptor for RuV. However, RuV bound to MOG-negative cells in a Ca2+ -independent manner. Collectively, our data demonstrate that RuV has two distinct binding mechanisms: one is Ca2+ -dependent and the other Ca2+ -independent. Ca2+ -dependent binding observed in lymphoid cells occurs by the direct interaction between E1 protein fusion loops and SM/Chol-enriched membranes. Clarification of the mechanism of Ca2+ -independent RuV binding is an important next step in understanding the pathology of RuV infection. IMPORTANCE Rubella has a significant impact on public health as infection during early pregnancy can result in babies being born with congenital rubella syndrome. Despite effective rubella vaccines being available, rubella outbreaks still occur in many countries. We studied the entry mechanism of Rubella virus (RuV) and found that RuV binds directly to the host plasma membrane in the presence of Ca2+ at neutral pH. This Ca2+ -dependent binding is specifically directed to membranes enriched in sphingomyelin and cholesterol, and is critical for RuV infection. Importantly, RuV also binds to many cell lines in a Ca2+ -independent manner. An unidentified RuV receptor(s) is involved in this Ca2+ -independent binding. We believe that the data presented here may aid the development of the first anti-RuV drug.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app