A challenge for HIV-1 immunogen design is inducing neutralizing antibodies (NAbs) against neutralization-resistant (Tier-2) viruses that dominate human transmissions. We show that a soluble recombinant HIV-1 envelope glycoprotein trimer that adopts a native conformation (BG505 SOSIP.664) induced NAbs potently against the sequence-matched Tier-2 virus in rabbits and similar but weaker responses in macaques. The trimer also consistently induced cross-reactive NAbs against more sensitive (Tier-1) viruses. Tier-2 NAbs recognized conformational epitopes that differed between animals and in some cases overlapped with those recognized by broadly neutralizing antibodies (bNAbs), whereas Tier-1 responses targeted linear V3 epitopes. A second trimer, B41 SOSIP.664, also induced a strong autologous Tier-2 NAb response in rabbits. Thus, native-like trimers represent a promising starting point for developing HIV-1 vaccines aimed at inducing bNAbs.

Herpes simplex virus (HSV) anterograde transport in neuronal axons is vital, allowing spread from latently infected ganglia to epithelial tissues, where viral progeny are produced in numbers allowing spread to other hosts. The HSV membrane proteins gE/gI and US9 initiate the process of anterograde axonal transport, ensuring that virus particles are transported from the cytoplasm into the most proximal segments of axons. These proteins do not appear to be important once HSV is inside axons. We previously described HSV double mutants lacking both gE and US9 that failed to transport virus particles into axons. Here we show that gE US9 double mutants accumulate large quantities of unenveloped and partially enveloped capsids in neuronal cytoplasm. These defects in envelopment can explain the defects in axonal transport of enveloped virions. In addition, the unenveloped capsids that accumulated were frequently bound to cytoplasmic membranes, apparently immobilized in intermediate stages of envelopment. A gE-null mutant produced enveloped virions, but these accumulated in large numbers in the neuronal cytoplasm rather than reaching cell surfaces as wild-type HSV virions do. Thus, in addition to the defects in envelopment, there was missorting of capsids and enveloped particles in the neuronal cytoplasm, which can explain the reduced anterograde transport of unenveloped capsids and enveloped virions. These mechanisms differ substantially from existing models suggesting that gE/gI and US9 function by tethering HSV particles to kinesin microtubule motors. The defects in assembly of gE US9 mutant virus particles were novel because they were neuron specific, in keeping with observations that US9 is neuron specific. Herpes simplex virus (HSV) and other alphaherpesviruses, such as varicella-zoster virus, depend upon the capacity to navigate in neuronal axons. To do this, virus particles tether themselves to dyneins and kinesins that motor along microtubules from axon tips to neuronal cell bodies (retrograde transport) or from cell bodies to axon tips (anterograde transport). This transit in axons is essential for alphaherpesviruses to establish latency in ganglia and then to reactivate and move back to peripheral tissues for spread to other hosts. Anterograde transport of HSV requires two membrane proteins: gE/gI and US9. Our studies reveal new mechanisms for how gE/gI and US9 initiate anterograde axonal transport. HSV mutants lacking both gE and US9 fail to properly assemble enveloped virus particles in the cytoplasm, which blocks anterograde transport of enveloped particles. In addition, there are defects in the sorting of virus particles such that particles, when formed, do not enter proximal axons.

A newly abundant Gracilaria species in the sounds of southeastern North Carolina has become a problem for commercial fishing and industries drawing water from the lower Cape Fear River. DNA sequence analyses have shown that this species is Gracilaria vermiculophylla, a taxon originally described from East Asia. Surveys for G. vermiculophylla have shown that it has a discontinuous distribution in the sounds of southeastern North Carolina, and suggest that it is spreading. Gracilaria vermiculophylla meets 6 of the 10 criteria used to help identify invasive species in that it has only recently appeared in southeastern North Carolina; is associated with human mechanisms of dispersal; has a restricted distribution; has disjunct populations in isolated oceans; no means of active dispersal, and an exotic evolutionary origin. The species may also meet two additional criteria as its local range is believed to be expanding, and it is filling a previously unoccupied seasonal niche. These factors taken together strongly suggest that G. vermiculophylla is an invasive species in southeastern North Carolina.

The nociceptin/orphanin FQ (NOP) receptor, the fourth member of the opioid receptor family, is involved in many processes common to the opioid receptors including pain and drug abuse.

Novel approaches are needed for overcoming barriers to successful association of herbaceous legumes with grasses in warm‐climate pastures and to identify low‐cost, long‐term solutions to the problem of N limitation in low‐input systems. The objective of this experiment was to evaluate defoliation management options during the year of establishment when rhizoma peanut (RP) (Arachis glabrata Benth.) was strip planted into existing bahiagrass (Paspalum notatum Flüggé). Treatments were four defoliation strategies: (i) Control (no defoliation of the planted RP strip and adjacent bahiagrass harvested for hay), (ii) Hay Production (RP strip and adjacent bahiagrass harvested for hay every 28 d), (iii) Simulated Continuous Stocking (pastures grazed weekly), and (iv) Rotational Stocking (pastures grazed every 28 d). Simulated Continuous and Rotational Stocking reduced RP canopy cover and frequency of occurrence. Greatest RP cover during the establishment year was achieved in August with 32 and 29% for the Control and Hay Production treatments compared to 5 and 4% for Simulated Continuous and Rotational Stocking, respectively. Spread of RP was least in Simulated Continuous Stocking. Light penetration to the level of RP in the canopy was not a primary driver of RP response because it was greatest for grazed plots where RP performed poorest. Results show that defoliation management during the establishment year is critical and if pastures are defoliated, hay production is the recommended option.