The NKG2D receptor is expressed on the surface of NK, T, and macrophage lineage cells and plays an important role in antiviral and antitumor immunity. To evade NKG2D recognition, herpesviruses block the expression of NKG2D ligands on the surface of infected cells using a diverse repertoire of sabotage methods. Cowpox and monkeypox viruses have taken an alternate approach by encoding a soluble NKG2D ligand, the orthopoxvirus major histocompatibility complex (MHC) class I-like protein (OMCP), which can block NKG2D-mediated cytotoxicity. This approach has the advantage of targeting a single conserved receptor instead of numerous host ligands that exhibit significant sequence diversity. Here, we show that OMCP binds the NKG2D homodimer as a monomer and competitively blocks host ligand engagement. We have also determined the 2.25-Å-resolution crystal structure of OMCP from the cowpox virus Brighton Red strain, revealing a truncated MHC class I-like platform domain consisting of a beta sheet flanked with two antiparallel alpha helices. OMCP is generally similar in structure to known host NKG2D ligands but has notable variations in regions typically used to engage NKG2D. Additionally, the determinants responsible for the 14-foldhigher affinity of OMCP for human than for murine NKG2D were mapped to a single loop in the NKG2D ligand-binding pocket.

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fax 01-972-952-9435. Abstract Acid stimulation treatments performed in the Upper Terminal (UT) Zone of the Wilmington Fiel~Los Angeles County, CA have been effective in removing formation damage caused by scale and fines migration. Unfortunately, most treatments have an average life of less than six months.A new Chemically Modified Acid (CMA) system has been implemented that utilizes a phosphoric acid in conjunction with hydrofluoric acid. This CMA system is pumped with a standard hydrochloric acid preflush and postflush.The phosphoric acid reacts with aluminum in clays and feldspars to form a temporary "protective film", thus allowing deeper penetration and more effective reaction of hydrofluoric acid on migratory silicates. Ahnninosilicate volubility is not eliminate but is controlled to allow a more uniform reaction. Another possible side benefit of the phosphoric acid is its ability to inhibit the formation of calcium carbonate scale.Initial production rates of the wells acidized with this new acid system are approximately the same as wells previously treated with 9'XO HC1:1'% HF, indicating removal of the damage. However, the real test of time has shown that the wells treated with this new system are producing at flatter decline rates, indicating either removal of additional fines or scale inhibition or both. Field data presented indicate an extension in the time to return to pre-treatment production rates from less than five months to more than nine months.Laboratory data are presented that shows the improved volubility and deeper penetration of this acid system over conventional HC1:HF. Post-acid job flowback samples were also analyzed to determine the extent of silicate dissolution and to investigate the possibility of scale inhibition.

As a K’awaika & Diné, I revisit my writings to answer a life-informing question, as opposed to just a research question, of how relationships inform and disrupt my meaning-making of being unapologetically Indigenous in the academy. To answer this question, I offer a series of personal stories and relatives to reconnect to what it means to navigate the doctoral process. Through relationality as a methodology, I connect two sets of stories to disrupt the linear and forward-moving underpinnings of the doctoral process. I connect stories to highlight three dimensions, i.e., authenticity, vulnerability, and intentionality, to develop what it means to be unapologetically Indigenous in the academy.

The genome of cowpoxvirus (CPXV) could be considered prototypical for orthopoxviridae (OXPV) since it contains many open reading frames (ORFs) absent or lost in other OPXV, including vaccinia virus (VACV). These additional ORFs are non-essential for growth in vitro but are expected to contribute to the broad host range, virulence and immune evasion characteristics of CPXV. For instance, unlike VACV, CPXV encodes proteins that interfere with T cell stimulation, either directly or by preventing antigen presentation or co-stimulation. When studying the priming of naïve T cells, we discovered that CPXV, but not VACV, encodes a secreted factor that interferes with activation and proliferation of naïve CD8+ and CD4+ T cells, respectively, in response to anti-CD3 antibodies, but not to other stimuli. Deletion mapping revealed that the inhibitory protein is encoded by CPXV14, a small secreted glycoprotein belonging to the poxvirus immune evasion (PIE) family and containing a smallpoxvirus encoded chemokine receptor (SECRET) domain that mediates binding to chemokines. We demonstrate that CPXV14 inhibition of antibody-mediated T cell activation depends on the presence of Fc-gamma receptors (FcγRs) on bystander cells. In vitro, CPXV14 inhibits FcγR-activation by antigen/antibody complexes by binding to FcγRs with high affinity and immobilized CPXV14 can trigger signaling through FcγRs, particularly the inhibitory FcγRIIB. In vivo, CPXV14-deleted virus showed reduced viremia and virulence resulting in reduced weight loss and death compared to wildtype virus whereas both antibody and CD8+ T cell responses were increased in the absence of CPXV14. Furthermore, no impact of CPXV14-deletion on virulence was observed in mice lacking the inhibitory FcγRIIB. Taken together our results suggest that CPXV14 contributes to virulence and immune evasion by binding to host FcγRs.

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