Abstract
HIV envelope glycoprotein is the most heavily glycosylated viral protein complex identified with over 20 glycans on its surface. This glycan canopy is thought to primarily shield the virus from host immune recognition as glycans are poor immunogens in general, however rare HIV neutralizing antibodies nevertheless potently recognize the glycan epitopes. While CD4 and chemokine receptors have been known as viral entry receptor and coreceptor, for many years the role of viral glycans in HIV entry was controversial. Recently, we showed that HIV envelope glycan binds to L-selectin in solution and on CD4 T lymphocytes. The viral glycan and L-selectin interaction functions to facilitate the viral adhesion and entry. Upon entry, infected CD4 T lymphocytes are stimulated to progressively shed L-selectin and suppressing this lectin receptor shedding greatly reduced HIV viral release and caused aggregation of diminutive virus-like particles within experimental infections and from infected primary T lymphocytes derived from both viremic and aviremic individuals. As shedding of L-selectin is mediated by ADAM metalloproteinases downstream of host-cell stimulation, these findings showed a novel mechanism for HIV viral release and offer a potential new class of anti-HIV compounds.
Highlights
Many phases of the HIV lifecycle, including the viral entry, reverse transcription and integration, viral gene transcription, translation and replication, and viral release and maturation, have been intensely studied over the years and targeted by the development of highly active antiretroviral therapies (HAART/ART; Deeks et al, 2015)
Upon viral entry, infected T cells loose L-selectin expression through both receptor internalization and shedding by ADAM metalloproteinases and the inhibition of L-selectin shedding resulted in budding virions aggregation, impaired the viral release in experimental infections and reduced viral RNA released from ART-suppressed viral reservoirs (Kononchik et al, 2018)
It is likely that both L-selectin internalization and shedding occur at different stages of HIV infections
Summary
Many phases of the HIV lifecycle, including the viral entry, reverse transcription and integration, viral gene transcription, translation and replication, and viral release and maturation, have been intensely studied over the years and targeted by the development of highly active antiretroviral therapies (HAART/ART; Deeks et al, 2015). L-selectin shedding appears required for HIV release from infected cells (Kononchik et al, 2018). Mechanistic work showed that mere binding of viral envelope gp120 protein to CD4 and CXCR4 was sufficient to induce down regulation in L-selectin expression (Marschner et al, 1999; Wang et al, 2004).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
