CCL28 Induces Mucosal Homing of HIV-1-Specific IgA-Secreting Plasma Cells in Mice Immunized with HIV-1 Virus-Like Particles

Mucosae-associated epithelial chemokine (MEC or CCL28) binds to CCR3 and CCR10 and recruits IgA-secreting plasma cells (IgA-ASCs) in the mucosal lamina propria. The ability of this chemokine to enhance migration of IgA-ASCs to mucosal sites was assessed in a mouse immunization model using HIV-1IIIB Virus-like particles (VLPs). Mice receiving either HIV-1IIIB VLPs alone, CCL28 alone, or the irrelevant CCL19 chemokine were used as controls. Results showed a significantly increased CCR3 and CCR10 expression on CD19+ splenocytes of HIV-1IIIB VPL-CCL28-treated mice. HIV-1 Env-specific IFN-γ, IL-4 and IL-5 production, total IgA, anti-Env IgA as well as gastro-intestinal mucosal IgA-secreting plasma cells were also significantly augmented in these mice. Notably, sera and vaginal secretions from HIV-1IIIB VLP-CCL28-treated mice exhibited an enhanced neutralizing activity against both a HIV-1/B-subtype laboratory strain and a heterologous HIV-1/C-subtype primary isolate. These data suggest that CCL28 could be useful in enhancing the IgA immune response that will likely play a pivotal role in prophylactic HIV vaccines

Identification of tRNAs incorporated into wild-type and mutant human immunodeficiency virus type 1.

We have identified the tRNAs which are incorporated into both wild-type human immunodeficiency virus type 1 strain IIIB (HIV-1IIIB) produced in COS-7 cells transfected with HIV-1 proviral DNA and mutant, noninfectious HIV-1Lai particles produced in a genetically engineered Vero cell line. The mutant proviral DNA contains nucleotides 678 to 8944; i.e., both long terminal repeats and the primer binding site are absent. As analyzed by two-dimensional polyacrylamide gel electrophoresis, both mutant and wild-type HIV-1 contain four major-abundance tRNA species, which include tRNA(1,2Lys), tRNA(3Lys) (the putative primer for HIV-1 reverse transcriptase) and tRNA(Ile). Identification was accomplished by comparing the electrophoretic mobilities and RNase T1 digests with those of tRNA(3Lys) and tRNA(1,2Lys) purified from human placenta and comparing the partial nucleotide sequence at the 3' end of each viral tRNA species with published tRNA sequences. Thus, the absence of the primer binding site in the mutant virus does not affect tRNA(Lys) incorporation into HIV-1. However, only the wild-type virus contains tRNA(3Lys) tightly associated with the viral RNA genome. The identification of the tightly associated tRNA as tRNA(3Lys) is based upon an electrophoretic mobility identical to that of tRNA(3Lys) and the ability of this RNA to hybridize with a tRNA(3Lys)-specific DNA probe. In addition to the four wild-type tRNA species, the mutant HIV-1-like particle contains two tRNA(His) species and three tRNA-sized species that we have been unable to identify. Their absence in wild-type virus makes it unlikely that they are required for viral infectivity

PCBs in the arctic atmosphere : I : spatial and temporal trends : 1992-1994.

In 1992, a long term program was established to measure the airborne concentrations of persistent organic pollutants (POPs) in the Arctic. To maximize spatial variation over a wide geographical area, three Arctic locations were selected; two sites in Canada, Alert on Ellesmere Island and Tagish in the western Yukon, and one in Russia at Dunai Island in eastern Siberia. PCB data is presented here for the years 1992−1994. Mean ∑PCB concentrations for 1993, the year when all three sites were running simultaneously, were 27.4, 17.0, and 34.0 pg/m3 at the Alert, Tagish, and Dunai sites, respectively. With the exception of the Tagish site in 1993, where ∑PCB concentrations were found to be weakly correlated with mean monthly tem peratures, no correlation with temperature was observed. However, changes in the homolog group profile with temperature were apparent. On an annual basis, the trichlorinated congeners made the largest single contribution to the atmospheric concentrations of ∑PCB, however, this contribution declined with the onset of warmer months. This temperature-dependent homolog pattern was most clearly evident at Dunai, where the contribution of the pentachlorinated congeners matched or exceeded that of the trichlorinated congeners during May, June, and July of 1993. It was also evident at Alert and Tagish, but not to the same degree. Spatial and year-to-year differences at these Arctic sites were attributed to both the site's proximity to source areas (where different PCB mixtures and quantities have been used) and to the influence of air mass movement from these source regions

Multi-year observations of organohalogen pesticides in the arctic atmosphere.

Atmospheric measurements of organohalogen pesticides (OCs) have been made in both the Canadian and Russian Arctic. A full quality-controlled database of weekly samples is now available for the years 1992–94. Hexachlorobenzene (HCB) and the hexachlorocyclohexanes (HCHs) were the most predominant compounds in the atmosphere, followed by the chlordanes and endosulfan. Evidence of a seasonality in air concentrations was apparent particularly for the pesticide metabolites, compounds such as oxychlordane, heptachlor epoxide and dieldrin showing a significant positive correlation with temperature (p<0.01). An exception to this was p, p′-DDE which showed elevated levels during the winter. Large spatial differences in mean annual concentrations of most OCs were not evident; however, spatial differences were apparent in α/γ-HCH ratios between the high Arctic site of Alert and the Yukon site of Tagish. The influence of both the European sector and the regional effect of the Arctic Ocean on the high Arctic probably accounted for this difference. A decline in the trans-chlordane/cis-chlordane ratio compared to studies during the 1980s may indicate a more weathered source of chlordane to be present in the Arctic by the mid-1990s. Slopes generated from plots of partial pressure (ln P) versus 1/T for selected compounds were considerably less steep than those derived from temperate studies. It is inferred here that long-range transport has a large influence on contaminant levels in the arctic atmosphere