IgG Fc Receptors Provide an Alternative Infection Route for Murine Gamma-Herpesvirus-68

BACKGROUND: Herpesviruses can be neutralized in vitro but remain infectious in immune hosts. One difference between these settings is the availability of immunoglobulin Fc receptors. The question therefore arises whether a herpesvirus exposed to apparently neutralizing antibody can still infect Fc receptor(+) cells. PRINCIPAL FINDINGS: Immune sera blocked murine gamma-herpesvirus-68 (MHV-68) infection of fibroblasts, but failed to block and even enhanced its infection of macrophages and dendritic cells. Viral glycoprotein-specific monoclonal antibodies also enhanced infection. MHV-68 appeared to be predominantly latent in macrophages regardless of whether Fc receptors were engaged, but the infection was not abortive and new virus production soon overwhelmed infected cultures. Lytically infected macrophages down-regulated MHC class I-restricted antigen presentation, endocytosis and their response to LPS. CONCLUSIONS: IgG Fc receptors limit the neutralization of gamma-herpesviruses such as MHV-68

Acidification in the Cairngorms and Lochnagar: a palaeoecological assessment

Sensitive lakes in areas of the United Kingdom with moderate to high sulphur deposition have been acidified since the middle of the nineteenth century- (Battarbee et al. 1988). Regions such as Galloway, south west Scotland (eg. Flower and Battarbee 1983, Flower et al. 1987), Wales (eg. Battarbee et al. 1988, Fritz et aL 1990), Cumbria (eg. Battarbee et al 1988, Atkinson and Haworth 1990), and Rannoch Moor in the central Scottish Highlands (eg. Flower et al 1988) have been affected. This study extends the geographical survey of lake acidification to the Caimgorm and Lochnagar regions of north east Scotland (Figure 1). The Caimgorms and Lochnagar are areas of considerable conservation value, forming the largest single area of land over 1000 m in the UK. The Caimgorm mountain plateau is a National Nature Reserve, noted for its alpine flora and fauna, whilst the Lochnagar range is a Scottish Wildlife Trust reserve. A secondary- aim of the study was to evaluate the 11land-use 11 hypothesis (eg. Rosenqvist 1977, 1978, 1981) as a mechanism for lake acidification by examining high altitude sites with no active land-management. Sites selected are all remote, lie above the tree line and have undisturbed catchments. Lochnagar and the Caimgorms are situated on sensitive granite geology (Kinniburgh and Edmunds 1986, Wells et al. 1986) in an area of moderate acid deposition (c. 0.95 g S yr-1 ). It can be predicted that sensitive lakes in this area (those having Ca2 + values of <60 μeq i-1 ) will have acidified (Battarbee 1989)

Palaeoecological evaluation of the recent acidification of Lochnagar, Scotland

Lochnagar, a high altitude, relatively deep, come lake, lies on the Royal Deeside ESUHC of Balmoral, in an area which experiences moderate levels of acid deposition, The loch catchment comprises granite bedrock and is dominated by bare rock but overlain in places with blanket peals, Lochnagar may thus be considered potentially susceptible to acidification, The contemporary pH of the loch water is c. 5,0

Pre-transplant CDKN2A expression in kidney biopsies predicts renal function and is a future component of donor scoring criteria

CDKN2A is a proven and validated biomarker of ageing which acts as an off switch for cell proliferation. We have demonstrated previously that CDKN2A is the most robust and the strongest pre-transplant predictor of post- transplant serum creatinine when compared to “Gold Standard” clinical factors, such as cold ischaemic time and donor chronological age. This report shows that CDKN2A is better than telomere length, the most celebrated biomarker of ageing, as a predictor of post-transplant renal function. It also shows that CDKN2A is as strong a determinant of post-transplant organ function when compared to extended criteria (ECD) kidneys. A multivariate analysis model was able to predict up to 27.1% of eGFR at one year post-transplant (p = 0.008). Significantly, CDKN2A was also able to strongly predict delayed graft function. A pre-transplant donor risk classification system based on CDKN2A and ECD criteria is shown to be feasible and commendable for implementation in the near future

Post-Exposure Vaccination Improves Gammaherpesvirus Neutralization

Herpesvirus carriers transmit infection despite making virus-specific antibodies. Thus, their antibody responses are not necessarily optimal. An important question for infection control is whether vaccinating carriers might improve virus neutralization. The antibody response to murine gamma-herpesvirus-68 (MHV-68) blocks cell binding, but fails to block and even enhances an IgG Fc receptor-dependent infection of myeloid cells. Viral membrane fusion therefore remains intact. Although gH/gL-specific monoclonal antibodies can block infection at a post-binding step close to membrane fusion, gH/gL is a relatively minor antibody target in virus carriers. We show here that gH/gL-specific antibodies can block both Fc receptor-independent and Fc receptor-dependent infections, and that vaccinating virus carriers with a gH/gL fusion protein improves their capacity for virus neutralization both in vitro and in vivo. This approach has the potential to reduce herpesvirus transmission