A novel full-length two-domain KIR2DL5A allele isolated in Zimbabwean samples: KIR2DL5A*0010104.

The novel allele KIR2DL5A*0010104 differs from that of KIR2DL5A*0010101 with eight single intronic nucleotide changes

Mucosal dendritic cells in HIV-1 susceptibility: a critical role for C-type lectin receptors

Sexual transmission is the major route of HIV-1 infection worldwide. The interaction of HIV-1 with mucosal dendritic cells (DCs) might determine HIV-1 susceptibility as well as initial antiviral immunity controlling virus in the chronic phase. Different DC subsets reside in mucosal tissues and express specific C-type lectin receptors (CLRs) that interact with HIV-1 with different outcomes. HIV-1 has been shown to subvert CLRs for viral transmission and immune evasion, whereas CLRs can also protect against HIV-1 infection. Here, we will discuss the role of CLRs in HIV-1 transmission and adaptive immunity, and how the CLRs dictate the function of DCs in infection. Ultimately, understanding the interplay between CLRs and HIV-1 will lead to targeted approaches in the search for preventative measure

Identification of 2 -(4 -N ,N -Di methyl aminop henyl) -5-methyl -1-phenethyl -1H-benzimidazole targeting HIV-1 CA capsid protein and inhibiting HIV-1 replication in cellulo

International audienceThe capsid (CA) subunit of the HIV-1 Gag polyprotein is involved in several steps of the viral cycle, from the assembly of new viral particles to the protection of the viral genome until it enters into the nucleus of newly infected cells. As such, it represents an interesting therapeutic target to tackle HIV infection. In this study, we screened hundreds of compounds with a low cost of synthesis for their ability to interfere with Gag assembly in vitro. Representatives of the most promising families of compounds were then tested for their ability to inhibit HIV-1 replication in cellulo. From these molecules, a hit compound from the benzimidazole family with high metabolic stability and low toxicity, 2-(4-N,N-dimethylaminophenyl)-5-methyl-1-phenethyl-1H-benzimidazole (696), appeared to block HIV-1 replication with an IC50 of 3 µM. Quantitative PCR experiments demonstrated that 696 does not block HIV-1 infection before the end of reverse transcription, and molecular docking confirmed that 696 is likely to bind at the interface between two monomers of CA and interfere with capsid oligomerization. Altogether, 696 represents a promising lead molecule for the development of a new series of HIV-1 inhibitors

MAVS genetic variation is associated with decreased HIV-1 replication in vitro and reduced cd4+ t cell infection in HIV-1-infected individuals

The mitochondrial antiviral protein MAVS is a key player in the induction of antiviral responses; however, human immunodeficiency virus 1 (HIV-1) is able to suppress these responses. Two linked single nucleotide polymorphisms (SNPs) in the MAVS gene render MAVS insensitive to HIV-1-dependent suppression, and have been shown to be associated with a lower viral load at set point and delayed increase of viral load during disease progression. Here, we studied the underlying mechanisms involved in the control of viral replication in individuals homozygous for this MAVS genotype. We observed that individuals with the MAVS minor genotype had more stable total CD4+ T cell counts during a 7-year follow up and had lower cell-associated proviral DNA loads. Genetic variation in MAVS did not affect immune activation levels; however, a significantly lower percentage of naïve CD4+ but not CD8+ T cells was observed in the MAVS minor genotype. In vitro HIV-1 infection of peripheral blood mononuclear cells (PBMCs) from healthy donors with the MAVS minor genotype resulted in decreased viral replication. Although the precise underlying mechanism remains unclear, our data suggest that the protective effect of the MAVS minor genotype may be exerted by the initiation of local innate responses affecting viral replication and CD4+ T cell susceptibility

MAVS Genetic Variation Is Associated with Decreased HIV-1 Replication In Vitro and Reduced CD4+ T Cell Infection in HIV-1-Infected Individuals

The mitochondrial antiviral protein MAVS is a key player in the induction of antiviral responses; however, human immunodeficiency virus 1 (HIV-1) is able to suppress these responses. Two linked single nucleotide polymorphisms (SNPs) in the MAVS gene render MAVS insensitive to HIV-1-dependent suppression, and have been shown to be associated with a lower viral load at set point and delayed increase of viral load during disease progression. Here, we studied the underlying mechanisms involved in the control of viral replication in individuals homozygous for this MAVS genotype. We observed that individuals with the MAVS minor genotype had more stable total CD4+ T cell counts during a 7-year follow up and had lower cell-associated proviral DNA loads. Genetic variation in MAVS did not affect immune activation levels; however, a significantly lower percentage of naïve CD4+ but not CD8+ T cells was observed in the MAVS minor genotype. In vitro HIV-1 infection of peripheral blood mononuclear cells (PBMCs) from healthy donors with the MAVS minor genotype resulted in decreased viral replication. Although the precise underlying mechanism remains unclear, our data suggest that the protective effect of the MAVS minor genotype may be exerted by the initiation of local innate responses affecting viral replication and CD4+ T cell susceptibility

A new stable isotope approach identifies the fate of ozone in plant-soil systems

We show that the stable isotope 18O can be used to trace ozone into different components of the plant–soil system at environmentally relevant concentrations. • We exposed plants and soils to 18O-labelled ozone and used isotopic enrichment in plant dry matter, leaf water and leaf apoplast, as well as in soil dry matter and soil water, to identify sites of ozone-derived 18O accumulation. • It was shown that isotopic accumulation rates in plants can be used to infer the location of primary ozone-reaction sites, and that those in bare soils are dependent on water content. However, the isotopic accumulation rates measured in leaf tissue were much lower than the modelled stomatal flux of ozone. • Our new approach has considerable potential to elucidate the fate and reactions of ozone within both plants and soils, at scales ranging from plant communities to cellular defence mechanisms