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Measles is a highly contagious airborne viral disease. It can lead to serious complications and death and is preventable by vaccination. The live-attenuated measles vaccine (LAMV) derived from a measles virus (MV) isolated in 1954 has been in use globally for six decades and protects effectively by providing a durable humoral and cell-mediated immunity. Our study addresses the temporal stability of epitopes on the viral surface glycoprotein hemagglutinin (H) which is the major target of MV-neutralizing antibodies. We investigated the binding of seven vaccine-induced MV-H-specific monoclonal antibodies (mAbs) to cell-free synthesized MV-H proteins derived from the H gene sequences obtained from a lung specimen of a fatal case of measles pneumonia in 1912 and an isolate from a current case. The binding of four out of seven mAbs to the H protein of both MV strains provides evidence of epitopes that are stable for more than 100 years. The binding of the universally neutralizing mAbs RKI-MV-12b and RKI-MV-34c to the H protein of the 1912 MV suggests the long-term stability of highly conserved epitopes on the MV surface. [ABSTRACT FROM AUTHOR]

Phosphoinositide 3-kinase (PI3K) γ has been implicated in a vast array of physiological settings including the activation of different leukocyte species and the regulation of myocardial contractility. Activation of PI3Kγ is primarily mediated by Gβy subunits of heterotrimeric G proteins, which are recognized by a p101 regulatory subunit. Here, we describe the identification and characterization of a novel regulatory subunit of PI3Kγ, which we termed p87PIKAP (PI3Kγ adapter protein of 87 kDa). It is homologous to p101 in areas that we have recently shown that they mediate binding to the catalytic p110γ subunit and to Gβγ. Like p101, p87PIKAP binds to both p11γ and Gβγ and mediates activation of p11γ downstream of G protein-coupled receptors. In contrast to p101, p87PIKAP is highly expressed in heart and may therefore be crucial to PI3Kγ cardiac function. Moreover, p87PIKAP and p101 are both expressed in dendritic cells, macrophages, and neutrophils, raising the possibility of regulatory subunit-dependent differences in PI3Kγ signaling within the same cell type. We further provide evidence that p87PIKAP physically interacts with phosphodiesterase (PDE) 3B, suggesting that p87PIKAP is also involved in the recently described noncatalytic scaffolding interaction of p110γ with PDE3B. However, coexpression of PDE3B and PI3Kγ subunits was not sufficient to reconstitute the regulatory effect of PI3Kγ on PDE3B activity observed in heart, implying further molecules to be present in the complex regulating PDE3B in heart. [ABSTRACT FROM AUTHOR]