Role of CCL3L1-CCR5 Genotypes in the Epidemic Spread of HIV-1 and Evaluation of Vaccine Efficacy

Polymorphisms in CCR5, the major coreceptor for HIV, and CCL3L1, a potent CCR5 ligand and HIV-suppressive chemokine, are determinants of HIV-AIDS susceptibility. Here, we mathematically modeled the potential impact of these genetic factors on the epidemic spread of HIV, as well as on its prevention.Ro, the basic reproductive number, is a fundamental concept in explaining the emergence and persistence of epidemics. By modeling sexual transmission among HIV+/HIV- partner pairs, we find that Ro estimates, and concordantly, the temporal and spatial patterns of HIV outgrowth are highly dependent on the infecting partners' CCL3L1-CCR5 genotype. Ro was least and highest when the infected partner possessed protective and detrimental CCL3L1-CCR5 genotypes, respectively. The modeling data indicate that in populations such as Pygmies with a high CCL3L1 gene dose and protective CCR5 genotypes, the spread of HIV might be minimal. Additionally, Pc, the critical vaccination proportion, an estimate of the fraction of the population that must be vaccinated successfully to eradicate an epidemic was <1 only when the infected partner had a protective CCL3L1-CCR5 genotype. Since in practice Pc cannot be >1, to prevent epidemic spread, population groups defined by specific CCL3L1-CCR5 genotypes might require repeated vaccination, or as our models suggest, a vaccine with an efficacy of >70%. Further, failure to account for CCL3L1-CCR5-based genetic risk might confound estimates of vaccine efficacy. For example, in a modeled trial of 500 subjects, misallocation of CCL3L1-CCR5 genotype of only 25 (5%) subjects between placebo and vaccine arms results in a relative error of approximately 12% from the true vaccine efficacy.CCL3L1-CCR5 genotypes may impact on the dynamics of the HIV epidemic and, consequently, the observed heterogeneous global distribution of HIV infection. As Ro is lowest when the infecting partner has beneficial CCL3L1-CCR5 genotypes, we infer that therapeutic vaccines directed towards reducing the infectivity of the host may play a role in halting epidemic spread. Further, CCL3L1-CCR5 genotype may provide critical guidance for optimizing the design and evaluation of HIV-1 vaccine trials and prevention programs

Viral metagenomics demonstrates that domestic pigs are a potential reservoir for Ndumu virus

BACKGROUND: The rising demand for pork has resulted in a massive expansion of pig production in Uganda. This has resulted in increased contact between humans and pigs. Pigs can act as reservoirs for emerging infectious diseases. Therefore identification of potential zoonotic pathogens is important for public health surveillance. In this study, during a routine general surveillance for African swine fever, domestic pigs from Uganda were screened for the presence of RNA and DNA viruses using a high-throughput pyrosequencing method. FINDINGS: Serum samples from 16 domestic pigs were collected from five regions in Uganda and pooled accordingly. Genomic DNA and RNA were extracted and sequenced on the 454 GS-FLX platform. Among the sequences assigned to a taxon, 53% mapped to the domestic pig (Sus scrofa). African swine fever virus, Torque teno viruses (TTVs), and porcine endogenous retroviruses were identified. Interestingly, two pools (B and C) of RNA origin had sequences that showed 98% sequence identity to Ndumu virus (NDUV). None of the reads had identity to the class Insecta indicating that these sequences were unlikely to result from contamination with mosquito nucleic acids. CONCLUSIONS: This is the first report of the domestic pig as a vertebrate host for Ndumu virus. NDUV had been previously isolated only from culicine mosquitoes. NDUV therefore represents a potential zoonotic pathogen, particularly given the increasing risk of human-livestock-mosquito contact

Study of the ion exchange selectivity of layered titanosilicate Na-3(Na,H)Ti2O2[Si2O6](2) center dot 2H(2)O, AM-4, for strontium

International audienceThis paper describes for the first time the sorption behaviour of a titanosilicate, AM-4, that exhibits an extremely high affinity for strontium in neutral and alkaline media. The ion exchange selectivity of this layered titanosilicate is explained in relation to the crystalline structure. The simple approach which consists in studying carefully the distribution of formal charges of oxygens in the anionic framework and calculating a normalized bond length in order to measure the ion stability in its site has enabled us to account for the AM-4 performances for the strontium remediation in competition with alkali and alkaline earth metal ions, The Sr uptake amounts as a function of the pH were determined, they can be correlated to the formal charges of Si-O-nbo. The effect of sodium, potassium, calcium and magnesium on the Sr2+ ions sorption was also studied in binary solutions Sr2+/Na+, Sr2+/K+, Sr2+/Ca2+, Sr2+/Mg2+. The determination of the equilibrium constant Sr2+/2Na(+) and of the ion competitive effects with adsorption data have shown that Ca2+ is the most efficient to reduce the uptake of Sr2+. The preliminary Kd values provide an indication that this exchanger may act as a sorber for groundwater and nuclear remediation applications

Study of the ion exchange selectivity of layered titanosilicate Na-3(Na,H)Ti2O2[Si2O6](2) center dot 2H(2)O, AM-4, for strontium

International audienceThis paper describes for the first time the sorption behaviour of a titanosilicate, AM-4, that exhibits an extremely high affinity for strontium in neutral and alkaline media. The ion exchange selectivity of this layered titanosilicate is explained in relation to the crystalline structure. The simple approach which consists in studying carefully the distribution of formal charges of oxygens in the anionic framework and calculating a normalized bond length in order to measure the ion stability in its site has enabled us to account for the AM-4 performances for the strontium remediation in competition with alkali and alkaline earth metal ions, The Sr uptake amounts as a function of the pH were determined, they can be correlated to the formal charges of Si-O-nbo. The effect of sodium, potassium, calcium and magnesium on the Sr2+ ions sorption was also studied in binary solutions Sr2+/Na+, Sr2+/K+, Sr2+/Ca2+, Sr2+/Mg2+. The determination of the equilibrium constant Sr2+/2Na(+) and of the ion competitive effects with adsorption data have shown that Ca2+ is the most efficient to reduce the uptake of Sr2+. The preliminary Kd values provide an indication that this exchanger may act as a sorber for groundwater and nuclear remediation applications