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Srinika Ranasinghe, Pedro A Lamothe, Damien Z Soghoian, Samuel W Kazer, Michael B Cole, Alex K Shalek, Nir Yosef, R Brad Jones, Faith Donaghey, Chioma Nwonu, Priya Jani, Gina M Clayton, Frances Crawford, Janice White, Alana Montoya, Karen Power, Todd M Allen, Hendrik Streeck, Daniel E Kaufmann, Louis J Picker, John W Kappler, Bruce D Walker
CD8(+) T cell recognition of virus-infected cells is characteristically restricted by major histocompatibility complex (MHC) class I, although rare examples of MHC class II restriction have been reported in Cd4-deficient mice and a macaque SIV vaccine trial using a recombinant cytomegalovirus vector. Here, we demonstrate the presence of human leukocyte antigen (HLA) class II-restricted CD8(+) T cell responses with antiviral properties in a small subset of HIV-infected individuals. In these individuals, T cell receptor β (TCRβ) analysis revealed that class II-restricted CD8(+) T cells underwent clonal expansion and mediated killing of HIV-infected cells...
October 18, 2016: Immunity
Stephen A Migueles, Mark Connors
CD8(+) T cells that recognize peptides presented by MHC class II molecules have been observed in a macaque SIV vaccine model. A new study by Ranasinghe et al. (2016) shows that virus-specific class-II-restricted CD8(+) T cells can be found in some HIV-infected patients.
October 18, 2016: Immunity
Fei Ling, Dan-Dan He, Wei Wang, Ya-Bin Jin, Hui-Ling Zhang
Background-Sterile alpha motif and histidine aspartate domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) is one of the novel restriction factors that potently supresses HIV-1 infection in myeloid cells at an early stage in the viral replication cycle. SAMHD1 activity is blocked by the action of viral accessory protein x (Vpx), which targets and recruits SAMHD1 for proteasomal degradation, in the SIVsm/HIV-2 lineage. Objective-The impact of SAMHD1 polymorphisms on viral replication in Chinese-origin rhesus macaques (CR) and cynomolgus macaques of Vietnamese origin (CM) have not been reported until now...
October 18, 2016: Current HIV Research
Karen Kerkhof, Vincent Sluydts, Somony Heng, Saorin Kim, Myrthe Pareyn, Laura Willen, Lydie Canier, Siv Sovannaroth, Didier Ménard, Tho Sochantha, Marc Coosemans, Lies Durnez
BACKGROUND: Malaria transmission is highly heterogeneous, especially in low endemic countries, such as Cambodia. This results in geographical clusters of residual transmission in the dry, low transmission season, which can fuel the transmission to wider areas or populations during the wet season. A better understanding of spatial clustering of malaria can lead to a more efficient, targeted strategy to reduce malaria transmission. This study aims to evaluate the potential of the use of serological markers to define spatial patterns in malaria exposure...
October 19, 2016: Malaria Journal
Meri Kankaanpää, Maria Raitakari, Leila Muukkonen, Siv Gustafsson, Merja Heitto, Ari Palomäki, Kimmo Suojanen, Veli-Pekka Harjola
BACKGROUND: To assess whether the use of point-of-care testing (POCT) and early assessment team (EAT) model shortens emergency department (ED) length of stay (LOS). METHODS: This prospective, observational study with comparison between three study periods was performed in three phases in a metropolitan ED with 57,000 annual visits. Data were collected from adult ambulatory patients who were discharged home. Phase 1 served as a control (n = 1559 in one month)...
October 18, 2016: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine
Susan Zolla-Pazner
No abstract text is available yet for this article.
October 23, 2016: AIDS
Siddappa N Byrareddy, James Arthos, Claudia Cicala, Francois Villinger, Kristina T Ortiz, Dawn Little, Neil Sidell, Maureen A Kane, Jianshi Yu, Jace W Jones, Philip J Santangelo, Chiara Zurla, Lyle R McKinnon, Kelly B Arnold, Caroline E Woody, Lutz Walter, Christian Roos, Angela Noll, Donald Van Ryk, Katija Jelicic, Raffaello Cimbro, Sanjeev Gumber, Michelle D Reid, Volkan Adsay, Praveen K Amancha, Ann E Mayne, Tristram G Parslow, Anthony S Fauci, Aftab A Ansari
Antiretroviral drug therapy (ART) effectively suppresses replication of both the immunodeficiency viruses, human (HIV) and simian (SIV); however, virus rebounds soon after ART is withdrawn. SIV-infected monkeys were treated with a 90-day course of ART initiated at 5 weeks post infection followed at 9 weeks post infection by infusions of a primatized monoclonal antibody against the α4β7 integrin administered every 3 weeks until week 32. These animals subsequently maintained low to undetectable viral loads and normal CD4(+) T cell counts in plasma and gastrointestinal tissues for more than 9 months, even after all treatment was withdrawn...
October 14, 2016: Science
A Sipahigil, R E Evans, D D Sukachev, M J Burek, J Borregaard, M K Bhaskar, C T Nguyen, J L Pacheco, H A Atikian, C Meuwly, R M Camacho, F Jelezko, E Bielejec, H Park, M Lončar, M D Lukin
Efficient interfaces between photons and quantum emitters form the basis for quantum networks and enable optical nonlinearities at the single-photon level. We demonstrate an integrated platform for scalable quantum nanophotonics based on silicon-vacancy (SiV) color centers coupled to diamond nanodevices. By placing SiV centers inside diamond photonic crystal cavities, we realize a quantum-optical switch controlled by a single color center. We control the switch using SiV metastable states and observe optical switching at the single-photon level...
October 13, 2016: Science
Christian Wächter, Lee E Eiden, Nedye Naumann, Candan Depboylu, Eberhard Weihe
BACKGROUND: The majority of investigations on HIV-associated neurocognitive disorders (HAND) neglect the cerebellum in spite of emerging evidence for its role in higher cognitive functions and dysfunctions in common neurodegenerative diseases. METHODS: We systematically investigated the molecular and cellular responses of the cerebellum as contributors to lentiviral infection-induced neurodegeneration, in the simian immunodeficiency virus (SIV)-infected rhesus macaque model for HIV infection and HAND...
October 14, 2016: Journal of Neuroinflammation
Xintao Hu, Antonio Valentin, Frances Dayton, Viraj Kulkarni, Candido Alicea, Margherita Rosati, Bhabadeb Chowdhury, Rajeev Gautam, Kate E Broderick, Niranjan Y Sardesai, Malcolm A Martin, James I Mullins, George N Pavlakis, Barbara K Felber
HIV sequence diversity and the propensity of eliciting immunodominant responses targeting variable regions of the HIV proteome are hurdles in the development of an effective AIDS vaccine. An HIV-derived conserved element (CE) p24(gag) plasmid DNA (pDNA) vaccine is able to redirect immunodominant responses to otherwise subdominant and often more vulnerable viral targets. By homology to the HIV immunogen, seven CE were identified in SIV p27(Gag) Analysis of 31 rhesus macaques vaccinated with full-length SIV gag pDNA showed inefficient induction (58% response rate) of cellular responses targeting these CE...
October 12, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Mohammed Asmal, Sophie Lane, Meijuan Tian, Gabrielle Nickel, Colin Venner, Brennan Dirk, Jimmy Dikeakos, Corinne Luedemann, Linh Mach, Harikrishnan Balachandran, Adam Buzby, Srinivas Rao, Norman Letvin, Yong Gao, Eric J Arts
For studies on vaccines and therapies for HIV disease, SIV-HIV chimeric viruses harboring the HIV-1 env gene (SHIVenv) remain the best virus in non-human primate models. However, there are still very few SHIVenv viruses that can cause AIDS in non-CD8-depleted animals. In the present study, a recently created CCR5-using SHIVenv_B3 virus with env gene derived from acute/early HIV-1 infections (AHI) successfully established pathogenic infection in macaques. Through a series of investigations on the evolution, mutational profile, and phenotype of the virus and the resultant humoral immune response in infected rhesus macaques, we found that the E32K mutation in the Env C1 domain was associated with macaque pathogenesis, and that the electrostatic interactions in Env may favor E32K at the gp120 N terminus and "lock" the binding to heptad repeat 1 of gp41 in the trimer and produce a SHIVenv with increased fitness and pathogenesis during macaque infections...
October 6, 2016: Virology
Pranjali Dalvi, Himanshu Sharma, Mahendran Chinnappan, Miles Sanderson, Julie Allen, Ruoxi Zeng, Augustine Choi, Amy O'Brien-Ladner, Navneet K Dhillon
Intravenous drug use is one of the major risk factors for HIV-infection in HIV-related pulmonary arterial hypertension patients. We previously demonstrated exaggerated pulmonary vascular remodeling with enhanced apoptosis followed by increased proliferation of pulmonary endothelial cells on simultaneous exposure to both opioids and HIV protein(s). Here we hypothesize that the exacerbation of autophagy may be involved in the switching of endothelial cells from an early apoptotic state to later hyper-proliferative state...
October 10, 2016: Autophagy
Brodie Miles, Shannon M Miller, Joy M Folkvord, David N Levy, Eva G Rakasz, Pamela J Skinner, Elizabeth Connick
During chronic HIV infection, viral replication is concentrated in secondary lymphoid follicles. Cytotoxic CD8 T cells control HIV replication in extrafollicular regions, but not in the follicle. Here, we show CXCR5hiCD44hiCD8 T cells are a regulatory subset differing from conventional CD8 T cells, and constitute the majority of CD8 T cells in the follicle. This subset, CD8 follicular regulatory T cells (CD8 TFR), expand in chronic SIV infection, exhibit enhanced expression of Tim-3 and IL-10, and express less perforin compared to conventional CD8 T cells...
October 2016: PLoS Pathogens
Jinbiao Liu, Qianhao Xiao, Runhong Zhou, Yong Wang, Qiaoyang Xian, Tongcui Ma, Ke Zhuang, Li Zhou, Deyin Guo, Xu Wang, Wen-Zhe Ho, Jieliang Li
Altered T-cell homeostasis, such as expansion of CD8(+) T cells to the secondary lymphatic compartments, has been suggested as a mechanism of HIV/simian immunodeficiency virus (SIV)-pathogenesis. However, the role of immune activation of CD8(+) T cells in the CD4/CD8 turnover and viral replication in these tissues is not completely understood. In this study, we compared the expression of immune activation markers (CD69 and HLA-DR) on CD8(+) T cells in the peripheral blood and lymph nodes (LNs) of SIV-infected/uninfected Chinese rhesus macaques...
2016: Frontiers in Immunology
Sovannaroth Siv, Arantxa Roca-Feltrer, Seshu Babu Vinjamuri, Denis Mey Bouth, Dysoley Lek, Mohammad Abdur Rashid, Ngau Peng By, Jean Popovici, Rekol Huy, Didier Menard
The Cambodian National Strategic Plan for Elimination of Malaria aims to move step by step toward elimination of malaria across Cambodia with an initial focus on Plasmodium falciparum malaria before achieving elimination of all forms of malaria, including Plasmodium vivax in 2025. The emergence of artemisinin-resistant P. falciparum in western Cambodia over the last decade has drawn global attention to support the ultimate goal of P. falciparum elimination, whereas the control of P. vivax lags much behind, making the 2025 target gradually less achievable unless greater attention is given to P...
October 5, 2016: American Journal of Tropical Medicine and Hygiene
Shengbin Li, Joy M Folkvord, Eva G Rakasz, Hadia M Abdelaal, Reece K Wagstaff, Katalin J Kovacs, Hyeon O Kim, Ryoko Sawahata, Samantha MaWhinney, David Masopust, Elizabeth Connick, Pamela J Skinner
: HIV- and simian immunodeficiency virus (SIV)-specific CD8(+) T cells are typically largely excluded from lymphoid B cell follicles where HIV- and SIV-producing cells are most highly concentrated, indicating that B cell follicles are somewhat of an immune privileged site. To gain insights into virus-specific follicular CD8(+) T cells, we determined the location and phenotype of follicular SIV-specific CD8(+) T cells in situ, the local relationship of these cells to Foxp3(+) cells, and effects of CD8 depletion on levels of follicular SIV-producing cells in chronically SIV infected rhesus macaques...
October 5, 2016: Journal of Virology
Sunil Kannanganat, Linda S Wyatt, Sailaja Gangadhara, Venkatesarlu Chamcha, Lynette S Chea, Pamela A Kozlowski, Celia C LaBranche, Lakshmi Chennareddi, Benton Lawson, Pradeep B J Reddy, Tiffany M Styles, Thomas H Vanderford, David C Montefiori, Bernard Moss, Harriet L Robinson, Rama Rao Amara
We tested, in rhesus macaques, the effects of a 500-fold range of an admixed recombinant modified vaccinia Ankara (MVA) expressing rhesus GM-CSF (MVA/GM-CSF) on the immunogenicity and protection elicited by an MVA/SIV macaque 239 vaccine. High doses of MVA/GM-CSF did not affect the levels of systemic envelope (Env)-specific Ab, but it did decrease the expression of the gut-homing receptor α4β7 on plasmacytoid dendritic cells (p < 0.01) and the magnitudes of Env-specific IgA (p = 0.01) and IgG (p < 0...
September 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Maximilian Muenchhoff, Emily Adland, Owen Karimanzira, Carol Crowther, Matthew Pace, Anna Csala, Ellen Leitman, Angeline Moonsamy, Callum McGregor, Jacob Hurst, Andreas Groll, Masahiko Mori, Smruti Sinmyee, Christina Thobakgale, Gareth Tudor-Williams, Andrew J Prendergast, Henrik Kloverpris, Julia Roider, Alasdair Leslie, Delane Shingadia, Thea Brits, Samantha Daniels, John Frater, Christian B Willberg, Bruce D Walker, Thumbi Ndung'u, Pieter Jooste, Penny L Moore, Lynn Morris, Philip Goulder
Disease-free infection in HIV-infected adults is associated with human leukocyte antigen-mediated suppression of viremia, whereas in the sooty mangabey and other healthy natural hosts of simian immunodeficiency virus (SIV), viral replication continues unabated. To better understand factors preventing HIV disease, we investigated pediatric infection, where AIDS typically develops more rapidly than in adults. Among 170 nonprogressing antiretroviral therapy-naïve children aged >5 years maintaining normal-for-age CD4 T cell counts, immune activation levels were low despite high viremia (median, 26,000 copies/ml)...
September 28, 2016: Science Translational Medicine
Ann Chahroudi, Guido Silvestri
A subset of HIV-infected children shows an unusually benign course of infection that recapitulates key immunological aspects of the natural SIV infection of sooty mangabeys (Muenchhoff et al.).
September 28, 2016: Science Translational Medicine
Elodie Cassan, Anne-Muriel Arigon-Chifolleau, Jean-Michel Mesnard, Antoine Gross, Olivier Gascuel
Recent experiments provide sound arguments in favor of the in vivo expression of the AntiSense Protein (ASP) of HIV-1. This putative protein is encoded on the antisense strand of the provirus genome and entirely overlapped by the env gene with reading frame -2. The existence of ASP was suggested in 1988, but is still controversial, and its function has yet to be determined. We used a large dataset of ∼23,000 HIV-1 and SIV sequences to study the origin, evolution, and conservation of the asp gene. We found that the ASP ORF is specific to group M of HIV-1, which is responsible for the human pandemic...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
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