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Targeting herpesvirus entry complex and fusogen glycoproteins with prophylactic and therapeutic agents.
- Source :
-
Trends in Microbiology . Aug2023, Vol. 31 Issue 8, p788-804. 17p. - Publication Year :
- 2023
-
Abstract
- At the core entry process of human herpesviruses (HHVs), the glycoprotein H and L (gHgL)-based entry complex (EC) induces conformational change (pre- to post-fusion) of the fusogen glycoprotein B (gB). Vaccines and neutralizing antibodies (nAbs) against EC and gB are tested in clinical trials to prevent HHV infection. New structures of pre-gB are shorter with different arrangements of domains compared to post-gB. From pre-gB to post-gB transition, domain I, II, and V flip around the center, while buried domian IV is exposed to form a crown. Vaccines comprising pre-gB are predicted to be more effective. The structures of ECs and their receptors continue to be determined, further uncovering new neutralizing epitopes and mechanisms while characterizing the molecular processes of HHV entry. Structure-based approaches in vaccine design include stabilizing pre-gB, refining the fusion signal transmission model, and identifying more potent nAbs. Herpesviruses are among the most successful viruses found in human populations. They establish lifelong latent infections, which are punctuated by recurrent reactivations. The entry process of herpesviruses into specific target cells requires a well-orchestrated teamwork involving multiple envelope glycoproteins. The conserved glycoprotein B (gB) is the membrane fusogen, of which conformational changes are induced by an entry complex (EC) consisting of at least gH and gL. Despite the high prevalence and heavy disease burdens associated with human herpesviruses (HHVs), vaccines against these pathogens are still lacking, except for varicella zoster virus (VZV). Recent advances in understanding the coordinated mechanisms of action of the key EC glycoproteins and fusogen will help to improve approaches for effective vaccine development and neutralizing antibody (nAb) screening. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0966842X
- Volume :
- 31
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- Trends in Microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 164859209
- Full Text :
- https://doi.org/10.1016/j.tim.2023.03.001