Fatal Immunopathogenesis by SIV/HIV-1 (SHIV) Containing a Variant Form of the HIV-1sf33 env Gene in Juvenile and Newborn Rhesus Macaques

AbstractSIV/HIV-1 (SHIV) chimeric clones, constructed by substituting portions of the pathogenic molecular clone SIVmac239 with counterpart portions from HIV-1 clones, provide a means to analyze functions of selected HIV-1 genes in vivo in nonhuman primates. Our studies focused on SHIVsf33, which contains the vpu, tat, rev, and env genes of the cytopathic, T-cell line tropic clone HIV-1sf33 (subtype-B); this clone has a premature stop codon in the vpu gene. In three juvenile macaques inoculated intravenously with SHIVsf33, low-level persistent infection was established; no disease was observed for a period of >2 years. However, at ∼16 months p.i., one of four SHIVsf33-infected juvenile macaques exhibited an increase in virus load, depletion of CD4+ T cells in peripheral blood and lymph nodes, and other symptoms of simian AIDS (SAIDS). Virus recovered from this animal in the symptomatic stage was designated SHIVsf33a (A, adapted); this virus displayed multiple amino acid sequence changes throughout the HIV-1 env gene compared with the input SHIVsf33 clone. Additionally, a mutation in all clones from SHIVsf33a restored the open reading frame for the vpu gene. In vitro evaluations in tissue-culture systems revealed that SHIVsf33a replicated to higher levels and exhibited greater cytopathicity than SHIVsf33. Furthermore cloned env genes for SHIVsf33a were more fusogenic in a cell-fusion assay compared with the env gene of the SHIVsf33. Intravenous inoculation of SHIVsf33a into juvenile and newborn macaques resulted in a rapid decline in CD4+ T cells to very low levels and development of a fatal AIDS-like disease. A cell-free preparation of this pathogenic chimeric virus also established persistent infection when applied to oral mucosal membranes of juvenile macaques and produced a fatal AIDS-like disease. These studies on pathogenic SHIVsf33a establish the basis for further investigations on the role of the HIV-1 env gene in virus adaptation and in mechanism(s) of immunodeficiency in primates; moreover, the chimeric virus SHIVsf33a can play a role in elucidating mucosal membrane transmission and development of antiviral vaccines in newborns as well as juvenile and adult macaques

The CLIC Potential for New Physics

The Compact Linear Collider (CLIC) is a mature option for the future of high energy physics. It combines the benefits of the clean environment of $e^+e^-$ colliders with operation at high centre-of-mass energies, allowing to probe scales beyond the reach of the Large Hadron Collider (LHC) for many scenarios of new physics. This places the CLIC project at a privileged spot in between the precision and energy frontiers, with capabilities that will significantly extend knowledge on both fronts at the end of the LHC era. In this report we review and revisit the potential of CLIC to search, directly and indirectly, for physics beyond the Standard Model

Muon Collider Physics Summary

The perspective of designing muon colliders with high energy and luminosity,which is being investigated by the International Muon Collider Collaboration,has triggered a growing interest in their physics reach. We present a concisesummary of the muon colliders potential to explore new physics, leveraging onthe unique possibility of combining high available energy with very precisemeasurements.<br

Muon Collider Physics Summary

The perspective of designing muon colliders with high energy and luminosity,which is being investigated by the International Muon Collider Collaboration,has triggered a growing interest in their physics reach. We present a concisesummary of the muon colliders potential to explore new physics, leveraging onthe unique possibility of combining high available energy with very precisemeasurements.<br

The physics case of a 3 TeV muon collider stage

In the path towards a muon collider with center of mass energy of 10 TeV ormore, a stage at 3 TeV emerges as an appealing option. Reviewing the physicspotential of such muon collider is the main purpose of this document. In orderto outline the progression of the physics performances across the stages, a fewsensitivity projections for higher energy are also presented. There are manyopportunities for probing new physics at a 3 TeV muon collider. Some of themare in common with the extensively documented physics case of the CLIC 3 TeVenergy stage, and include measuring the Higgs trilinear coupling and testingthe possible composite nature of the Higgs boson and of the top quark at the 20TeV scale. Other opportunities are unique of a 3 TeV muon collider, and stemfrom the fact that muons are collided rather than electrons. This isexemplified by studying the potential to explore the microscopic origin of thecurrent $g$-2 and $B$-physics anomalies, which are both related with muons.<br

The physics case of a 3 TeV muon collider stage

In the path towards a muon collider with center of mass energy of 10 TeV ormore, a stage at 3 TeV emerges as an appealing option. Reviewing the physicspotential of such muon collider is the main purpose of this document. In orderto outline the progression of the physics performances across the stages, a fewsensitivity projections for higher energy are also presented. There are manyopportunities for probing new physics at a 3 TeV muon collider. Some of themare in common with the extensively documented physics case of the CLIC 3 TeVenergy stage, and include measuring the Higgs trilinear coupling and testingthe possible composite nature of the Higgs boson and of the top quark at the 20TeV scale. Other opportunities are unique of a 3 TeV muon collider, and stemfrom the fact that muons are collided rather than electrons. This isexemplified by studying the potential to explore the microscopic origin of thecurrent $g$-2 and $B$-physics anomalies, which are both related with muons.<br

HE-LHC: The High-Energy Large Hadron Collider – Future Circular Collider Conceptual Design Report Volume 4

In response to the 2013 Update of the European Strategy for Particle Physics (EPPSU), the Future Circular Collider (FCC) study was launched as a world-wide international collaboration hosted by CERN. The FCC study covered an energy-frontier hadron collider (FCC-hh), a highest-luminosity high-energy lepton collider (FCC-ee), the corresponding 100 km tunnel infrastructure, as well as the physics opportunities of these two colliders, and a high-energy LHC, based on FCC-hh technology. This document constitutes the third volume of the FCC Conceptual Design Report, devoted to the hadron collider FCC-hh. It summarizes the FCC-hh physics discovery opportunities, presents the FCC-hh accelerator design, performance reach, and staged operation plan, discusses the underlying technologies, the civil engineering and technical infrastructure, and also sketches a possible implementation. Combining ingredients from the Large Hadron Collider (LHC), the high-luminosity LHC upgrade and adding novel technologies and approaches, the FCC-hh design aims at significantly extending the energy frontier to 100 TeV. Its unprecedented centre-of-mass collision energy will make the FCC-hh a unique instrument to explore physics beyond the Standard Model, offering great direct sensitivity to new physics and discoveries