Faculty Opinions recommendation of A fetal wave of human type 3 effector γδ cells with restricted TCR diversity persists into adulthood.

Currently, no plague vaccine exists in the United States for human use. The capsular antigen (Caf1 or F1) and two type 3 secretion system (T3SS) components, the low-calcium-response V antigen (LcrV) and the needle protein YscF, represent protective antigens ofYersinia pestis. We used a replication-defective human type 5 adenovirus (Ad5) vector and constructed recombinant monovalent and trivalent vaccines (rAd5-LcrV and rAd5-YFV) that expressed either the codon-optimizedlcrVor the fusion gene designatedYFV(consisting ofycsF,caf1, andlcrV). Immunization of mice with the trivalent rAd5-YFV vaccine by either the intramuscular (i.m.) or the intranasal (i.n.) route provided protection superior to that with the monovalent rAd5-LcrV vaccine against bubonic and pneumonic plague when animals were challenged withY. pestisCO92. Preexisting adenoviral immunity did not diminish the protective response, and the protection was always higher when mice were administered one i.n. dose of the trivalent vaccine (priming) followed by a single i.m. booster dose of the purified YFV antigen. Immunization of cynomolgus macaques with the trivalent rAd5-YFV vaccine by the prime-boost strategy provided 100% protection against a stringent aerosol challenge dose of CO92 to animals that had preexisting adenoviral immunity. The vaccinated and challenged macaques had no signs of disease, and the invading pathogen rapidly cleared with no histopathological lesions. This is the first report showing the efficacy of an adenovirus-vectored trivalent vaccine against pneumonic plague in mouse and nonhuman primate (NHP) models.

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Cryo-EM structure of human type-3 inositol triphosphate receptor reveals the presence of a self-binding peptide that acts as an antagonist

Journal of Biological Chemistry ◽

10.1074/jbc.ra119.011570 ◽

2020 ◽

Vol 295 (6) ◽

pp. 1743-1753 ◽

Cited By ~ 5

Author(s):

Caleigh M. Azumaya ◽

Emily A. Linton ◽

Caitlin J. Risener ◽

Terunaga Nakagawa ◽

Erkan Karakas

Keyword(s):

Calcium Signaling ◽

Metabolic Diseases ◽

Inositol Triphosphate ◽

Biological Processes ◽

Human Type ◽

Physiological Processes ◽

Molecular Determinant ◽

Specific Regulation ◽

Type 3

Calcium-mediated signaling through inositol 1,4,5-triphosphate receptors (IP3Rs) is essential for the regulation of numerous physiological processes, including fertilization, muscle contraction, apoptosis, secretion, and synaptic plasticity. Deregulation of IP3Rs leads to pathological calcium signaling and is implicated in many common diseases, including cancer and neurodegenerative, autoimmune, and metabolic diseases. Revealing the mechanism of activation and inhibition of this ion channel will be critical to an improved understanding of the biological processes that are controlled by IP3Rs. Here, we report structural findings of the human type-3 IP3R (IP3R-3) obtained by cryo-EM (at an overall resolution of 3.8 Å), revealing an unanticipated regulatory mechanism where a loop distantly located in the primary sequence occupies the IP3-binding site and competitively inhibits IP3 binding. We propose that this inhibitory mechanism must differ qualitatively among IP3R subtypes because of their diverse loop sequences, potentially serving as a key molecular determinant of subtype-specific calcium signaling in IP3Rs. In summary, our structural characterization of human IP3R-3 provides critical insights into the mechanistic function of IP3Rs and into subtype-specific regulation of these important calcium-regulatory channels.

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Evaluation of the human type 3 adenoviral dodecahedron as a vector to target acute myeloid leukemia

Molecular Therapy — Methods & Clinical Development ◽

10.1016/j.omtm.2020.11.009 ◽

2021 ◽

Vol 20 ◽

pp. 181-190

Author(s):

Benjamin Caulier ◽

Gaëlle Stofleth ◽

Dalil Hannani ◽

Mélanie Guidetti ◽

Véronique Josserand ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Human Type ◽

Type 3 ◽

Acute Myeloid

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Human Types 1 and 3 3α-Hydroxysteroid Dehydrogenases: Differential Lability and Tissue Distribution1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.86.2.7216 ◽

2001 ◽

Vol 86 (2) ◽

pp. 841-846 ◽

Cited By ~ 1

Author(s):

Isabelle Dufort ◽

Fernand Labrie ◽

Van Luu-The

Keyword(s):

Hacat Keratinocytes ◽

Human Embryonic Kidney ◽

Intact Cells ◽

Hek 293 ◽

Human Type ◽

Hydroxysteroid Dehydrogenases ◽

293 Cells ◽

Hydroxy Compounds ◽

Type 3

3α-Hydroxysteroid dehydrogenases (3α-HSDs) catalyze the conversion of 3-ketosteroids to 3α-hydroxy compounds. The best known 3α-HSD activity is the transformation of the most potent natural androgen, dihydrotestosterone, into 5α-androstan-3α,17β-diol (3α-diol), a compound having much lower activity. Previous reports show that 3α-HSDs are involved in the metabolism of glucocorticoids, progestins, prostaglandins, bile acid precursors, and xenobiotics. 3α-HSDs could, thus, play a crucial role in the control of a series of active steroid levels in target tissues. In the human, type 1 3α-HSD was first identified as human chlordecone reductase. Recently, we have isolated and characterized type 3 3α-HSD that shares 81.7% identity with human type 1 3α-HSD. The transfection of vectors expressing types 1 and 3 3α-HSD in transformed human embryonic kidney (HEK-293) cells indicates that both enzymes efficiently catalyze the transformation of dihydrotestosterone into 3α-diol in intact cells. However, when the cells are broken, the activity of type 3 3α-HSD is rapidly lost, whereas the type 1 3α-HSD activity remains stable. We have previously found that human type 5 17β-HSD which possesses 84% and 86% identity with types 1 and 3 3α-HSD, respectively, is also labile, whereas rodent enzymes such as mouse type 5 17β-HSD and rat 3α-HSD are stable after homogenization of the cells. The variable stability of different enzymatic activities in broken cell preparations renders the comparison of different enzymes difficult. RNA expression analysis indicates that human type 1 3α-HSD is expressed exclusively in the liver, whereas type 3 is more widely expressed and is found in the liver, adrenal, testis, brain, prostate, and HaCaT keratinocytes. Based on enzymatic characteristics and sequence homology, it is suggested that type 1 3α-HSD is an ortholog of rat 3α-HSD while type 3 3α-HSD, which must have diverged recently, seems unique to human and is probably more involved in intracrine activity.

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