Diversity considerations in HIV-1 vaccine selection

Globally, human immunodeficiency virus-type 1 (HIV-1) is extraordinarily variable, and this diversity poses a major obstacle to AIDS vaccine development. Currently, candidate vaccines are derived from isolates, with the hope that they will be sufficiently cross-reactive to protect against circulating viruses. This may be overly optimistic, however, given that HIV-1 envelope proteins can differ in more than 30% of their amino acids. To contend with the diversity, country-specific vaccines are being considered, but evolutionary relationships may be more useful than regional considerations. Consensus or ancestor sequences could be used in vaccine design to minimize the genetic differences between vaccine strains and contemporary isolates, effectively reducing the extent of diversity by half.     

New data on the status and distribution of the bush dog (Speothos venaticus): Evaluating its quality of protection and directing research efforts

The bush dog (Speothos venaticus), listed as CITES Appendix 1 - vulnerable, is a small (5-6 kg), rarely seen canid from Central and South America. The World Conservation Union Canid Specialist Group (IUCN CSG) recommended that research with this species focus on their basic ecology so that a data-driven conservation strategy can be formulated. Information on the bush dog, however, has been lacking since standard field techniques have had little or no success with this species. The S. venaticus Status and Distribution Survey was developed in an attempt to use indirect methodologies to determine the bush dog’s conservation status in the wild, its current distribution, and identify ecological needs by correlating habitat types to bush dog sightings. Survey responses and literature generated a database with 399 historic bush dog locations recorded between 1834 and 2004. These locational records were used to update the species’ range extent map, an important conservation planning tool. With year and precision of data accounted for, we analyzed land use coverage at known locations where bush dogs have historically been reported to evaluate the likelihood that the species persists in the area today. In addition, these locations provided training data for generation of potential distribution maps (i.e., areas of occupancy) using ecological niche modeling (i.e., Maximum Entropy) and bioclimatic data. These analyses revealed that 20% of the historic bush dog locations are associated with fragmented or altered habitat. These results allowed the status of bush dog habitat to be re-evaluated and areas that require more intensive research and protection to be identified.     

Structure of a V3-containing HIV-1 gp120 core

The third variable region (V3) of the HIV-1 gp120 envelope glycoprotein is immunodominant and contains features essential for coreceptor binding. We determined the structure of V3 in the context of an HIV-1 gp120 core complexed to the CD4 receptor and to the X5 antibody at 3.5 angstrom resolution. Binding of gp120 to cell-surface CD4 would position V3 so that its coreceptor-binding tip protrudes 30 angstroms from the core toward the target cell membrane. The extended nature and antibody accessibility of V3 explain its immunodominance. Together, the results provide a structural rationale for the role of V3 in HIV entry and neutralization.     

Pharmacokinetics of ponazuril after administration of a single oral dose to green turtles (Chelonia mydas)

The coccidian protozoan, Caryospora cheloniae, has been associated with severe enteritis and encephalitis in immature farm-raised green turtles (Chelonia mydas) in the Cayman Islands, immature green turtles off the coast of Florida, and immature stranded sea turtles in Australia. An effective anti-coccidial drug that is both orally absorbed and well-distributed throughout the body is needed for treatment of turtles diagnosed with coccidiosis in rehabilitation facilities. Ponazuril is a triazine antiprotozoal drug that is approved in the USA for the treatment of another Apicomplexan, Sarcocystis neurona, and has also been successfully used in the therapy of other coccidian parasites. The objective of this study was to perform an oral dose-ranging pilot study (10–100 mg/kg of body weight ponazuril) in green turtles (N = 9), followed by oral administration of ponazuril at 100 mg/kg body weight (N = 8) to assess its disposition. Another goal of this study was to optimize the method of oral drug administration to green turtles. Plasma ponazuril concentrations were quantified using high performance liquid chromatography (HPLC). Standard compartmental models were fit to the data. Ponazuril was absorbed after oral administration at 100 mg/kg BW, with a maximum plasma concentration of 3.3 µg/ml. Dose-dependent pharmacokinetic parameters only weakly correlated with the dose rate, apparently due to considerable pharmacokinetic variability observed between turtles. Administration of ponazuril in gelatin capsules using a balling gun was deemed the least variable and most successful method of drug administration. Further studies are needed to evaluate the safety and efficacy of ponazuril in sea turtles with coccidiosis.     

Paleoclimatic evidence for future ice-sheet instability and rapid sea-level rise

Sea-level rise from melting of polar ice sheets is one of the largest potential threats of future climate change. Polar warming by the year 2100 may reach levels similar to those of 130,000 to 127,000 years ago that were associated with sea levels several meters above modern levels; both the Greenland Ice Sheet and portions of the Antarctic Ice Sheet may be vulnerable. The record of past ice-sheet melting indicates that the rate of future melting and related sea-level rise could be faster than widely thought.     

Envelope-constrained neutralization-sensitive HIV-1 after heterosexual transmission

Heterosexual transmission accounts for the majority of human immunodeficiency virus-1 (HIV-1) infections worldwide, yet the viral properties that determine transmission fitness or outgrowth have not been elucidated. Here we show, for eight heterosexual transmission pairs, that recipient viruses were monophyletic, encoding compact, glycan-restricted envelope glycoproteins. These viruses were also uniquely sensitive to neutralization by antibody from the transmitting partner. Thus, the exposure of neutralizing epitopes, which are lost in chronic infection because of immune escape, appears to be favored in the newly infected host. This reveals characteristics of the envelope glycoprotein that influence HIV-1 transmission and may have implications for vaccine design.