8tqi
From Proteopedia
Hemagglutinin-neuraminidase from Human parainfluenza virus type 3: complex with rPIV3-23 and rPIV3-28 Fabs
Structural highlights
FunctionHN_PI3H4 Attaches the virus to sialic acid-containing cell receptors and thereby initiating infection. Binding of HN protein to the receptor induces a conformational change that allows the F protein to trigger virion/cell membranes fusion (By similarity). Neuraminidase activity ensures the efficient spread of the virus by dissociating the mature virions from the neuraminic acid containing glycoproteins (By similarity). Publication Abstract from PubMedHuman parainfluenza virus type 3 (hPIV3) is a respiratory pathogen that can cause severe disease in older people and infants. Currently, vaccines against hPIV3 are in clinical trials but none have been approved yet. The haemagglutinin-neuraminidase (HN) and fusion (F) surface glycoproteins of hPIV3 are major antigenic determinants. Here we describe naturally occurring potently neutralizing human antibodies directed against both surface glycoproteins of hPIV3. We isolated seven neutralizing HN-reactive antibodies and a pre-fusion conformation F-reactive antibody from human memory B cells. One HN-binding monoclonal antibody (mAb), designated PIV3-23, exhibited functional attributes including haemagglutination and neuraminidase inhibition. We also delineated the structural basis of neutralization for two HN and one F mAbs. MAbs that neutralized hPIV3 in vitro protected against infection and disease in vivo in a cotton rat model of hPIV3 infection, suggesting correlates of protection for hPIV3 and the potential clinical utility of these mAbs. Functional and structural basis of human parainfluenza virus type 3 neutralization with human monoclonal antibodies.,Suryadevara N, Otrelo-Cardoso AR, Kose N, Hu YX, Binshtein E, Wolters RM, Greninger AL, Handal LS, Carnahan RH, Moscona A, Jardetzky TS, Crowe JE Jr Nat Microbiol. 2024 Aug;9(8):2128-2143. doi: 10.1038/s41564-024-01722-w. Epub , 2024 Jun 10. PMID:38858594[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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