BackgroundHIV-1 clade C (HIV-C) predominates worldwide, and anti-HIV-C vaccines are urgently needed. Neutralizing antibody (nAb) responses are considered important but have proved difficult to elicit. Although some current immunogens elicit antibodies that neutralize highly neutralization-sensitive (tier 1) HIV strains, most circulating HIVs exhibiting a less sensitive (tier 2) phenotype are not neutralized. Thus, both tier 1 and 2 viruses are needed for vaccine discovery in nonhuman primate models.Methodology/Principal FindingsWe constructed a tier 1 simian-human immunodeficiency virus, SHIV-1157ipEL, by inserting an “early,” recently transmitted HIV-C env into the SHIV-1157ipd3N4 backbone [1] encoding a “late” form of the same env, which had evolved in a SHIV-infected rhesus monkey (RM) with AIDS. SHIV-1157ipEL was rapidly passaged to yield SHIV-1157ipEL-p, which remained exclusively R5-tropic and had a tier 1 phenotype, in contrast to “late” SHIV-1157ipd3N4 (tier 2). After 5 weekly low-dose intrarectal exposures, SHIV-1157ipEL-p systemically infected 16 out of 17 RM with high peak viral RNA loads and depleted gut CD4+ T cells. SHIV-1157ipEL-p and SHIV-1157ipd3N4 env genes diverge mostly in V1/V2. Molecular modeling revealed a possible mechanism for the increased neutralization resistance of SHIV-1157ipd3N4 Env: V2 loops hindering access to the CD4 binding site, shown experimentally with nAb b12. Similar mutations have been linked to decreased neutralization sensitivity in HIV-C strains isolated from humans over time, indicating parallel HIV-C Env evolution in humans and RM.Conclusions/SignificanceSHIV-1157ipEL-p, the first tier 1 R5 clade C SHIV, and SHIV-1157ipd3N4, its tier 2 counterpart, represent biologically relevant tools for anti-HIV-C vaccine development in primates.

A better understanding of the electrodynamic behavior of cells interacting with electric fields would allow for novel scientific insights and would lead to the next generation of cell manipulation, diagnostics, and treatment. Here, we introduce a promising electrode design by using metal oxide high-k dielectric passivation. The thermally generated dielectric passivation layer enables efficient electric field coupling to the fluid sample comprising cells while simultaneously decoupling the electrode ohmically from the electrolyte, allowing for better control and adjustability of electric field effects due to reduced electrochemical reactions at the electrode surface. This approach demonstrates cell-size specific lysis with electric fields in a microfluidic flow-through design resulting in 99.8% blood cell lysis at 6 s exposure without affecting the viability of Gram-positive and Gram-negative bacterial spike-ins. The advantages of this new approach can support next-generation investigations of electrodynamics in biological systems and their exploitation for cell manipulation in multiple fields of medicine, life science, and industry.

No abstract

No abstract

Capacitive coupling of electric fields diminishes energy dissipation and offers superior control over field parameters, resulting in predictable biological outcomes.