Genetic Variation in OAS1 Is a Risk Factor for Initial Infection with West Nile Virus in Man

West Nile virus (WNV) is a re-emerging pathogen that can cause fatal encephalitis. In mice, susceptibility to WNV has been reported to result from a single point mutation in oas1b, which encodes 2′–5′ oligoadenylate synthetase 1b, a member of the type I interferon-regulated OAS gene family involved in viral RNA degradation. In man, the human ortholog of oas1b appears to be OAS1. The ‘A’ allele at SNP rs10774671 of OAS1 has previously been shown to alter splicing of OAS1 and to be associated with reduced OAS activity in PBMCs. Here we show that the frequency of this hypofunctional allele is increased in both symptomatic and asymptomatic WNV seroconverters (Caucasians from five US centers; total n = 501; OR = 1.6 [95% CI 1.2–2.0], P = 0.0002 in a recessive genetic model). We then directly tested the effect of this SNP on viral replication in a novel ex vivo model of WNV infection in primary human lymphoid tissue. Virus accumulation varied markedly among donors, and was highest for individuals homozygous for the ‘A’ allele (P<0.0001). Together, these data identify OAS1 SNP rs10774671 as a host genetic risk factor for initial infection with WNV in humans

Distribution of Dengue Virus Types 1 and 4 in Blood Components from Infected Blood Donors from Puerto Rico

<div><p>Background</p><p>Dengue is a mosquito-borne viral disease caused by the four dengue viruses (DENV-1 to 4) that can also be transmitted by blood transfusion and organ transplantation. The distribution of DENV in the components of blood from infected donors is poorly understood.</p><p>Methods</p><p>We used an in-house TaqMan qRT-PCR assay to test residual samples of plasma, cellular components of whole blood (CCWB), serum and clot specimens from the same collection from blood donors who were DENV-RNA-reactive in a parallel blood safety study. To assess whether DENV RNA detected by TaqMan was associated with infectious virus, DENV infectivity in available samples was determined by culture in mosquito cells.</p><p>Results</p><p>DENV RNA was detected by TaqMan in all tested blood components, albeit more consistently in the cellular components; 78.8% of CCWB, 73.3% of clots, 86.7% of sera and 41.8% of plasma samples. DENV-1 was detected in 48 plasma and 97 CCWB samples while DENV-4 was detected in 21 plasma and 31 CCWB samples. In mosquito cell cultures, 29/111 (26.1%) plasma and 32/97 (32.7%) CCWB samples were infectious. A subset of samples from 29 donors was separately analyzed to compare DENV viral loads in the available blood components. DENV viral loads did not differ significantly between components and ranged from 3–8 log₁₀ PCR-detectable units/ml.</p><p>Conclusions</p><p>DENV was present in all tested components from most donors, and viral RNA was not preferentially distributed in any of the tested components. Infectious DENV was also present in similar proportions in cultured plasma, clot and CCWB samples, indicating that these components may serve as a resource when sample sizes are limited. However, these results suggest that the sensitivity of the nucleic acid tests (NAT) for these viruses would not be improved by testing whole blood or components other than plasma.</p></div

Developing and using the Neuroimaging and Data Sharing Data Model: the NIDASH Working Group

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Prevalence of SARS-CoV-2 Viremia in Presymptomatic Blood Donors in the Delta and Omicron Variant Eras

Presymptomatic plasma samples from 1596 donors reporting coronavirus disease 2019 infection or symptoms after blood donation were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and anti-S and anti-N antibodies. Prior infection and vaccination both protected from developing SARS-CoV-2 RNAemia and from symptomatic infection. RNAemia rates did not differ in the Delta and Omicron variant eras

Culture of DENV-positive blood components.

<p>A) Percentage of TaqMan-reactive cell culture supernatant from mosquito C6/36 cells infected with plasma (PL), the cellular component of whole blood (CCWB), serum (SE) or homogenized clots (CL) from samples from Puerto Rican blood donors, 2012–2013. B) Infectivity titers of DENV-1-positive PL or CCWB from samples from infected Puerto Rican blood donors, 2012–2013, in supernatants from a single passage in cultured mosquito C6/36 cells. C) Infectivity titers of DENV-4-positive PL or CCWB from samples from infected Puerto Rican blood donors, 2012–2013, in supernatants from a single passage in cultured mosquito C6/36 cells. For both B) and C), whiskers represent 10-90th percentile. Outliers are shown as black dots. Mean is shown as a “+” sign and median as a horizontal line inside the box.</p

Summary of DENV testing by TaqMan in plasma, cellular component of whole blood, serum and clot specimens from blood donors from Puerto Rico, 2012–2013, n = 165, and negative controls from the contiguous U.S., n = 16.

<p>Summary of DENV testing by TaqMan in plasma, cellular component of whole blood, serum and clot specimens from blood donors from Puerto Rico, 2012–2013, n = 165, and negative controls from the contiguous U.S., n = 16.</p

Linked comparison of DENV viral loads in blood components including clots.

<p>A) DENV-1 and DENV-4 combined viral loads in plasma (PL), the cellular component of whole blood (CCWB) and clot (CL), n = 29 samples. B) DENV-1 and DENV-4 combined viral loads in plasma (PL), the cellular component of whole blood (CCWB) and fresher clot (CL), n = 6 samples.</p

Detection of DENV RNA in blood components.

<p>A) DENV-1 and DENV-4 average viral load observed in plasma (PL), the cellular component of whole blood (CCWB), serum (SE) and homogenized clot specimens (CL). DENV viral load average in each sample co-component is expressed in log₁₀ PDU/mL. B) Ct value averages for DENV-1 and DENV-4 plasma (PL) and cellular component of whole blood (CCWB). Samples were collected from infected Puerto Rican blood donors, 2012–2013. Only samples with Ct values ≤38 were included in the quantitative analysis. Whiskers represent 10-90^th percentile. Outliers are shown as black dots. Mean is shown as a “+” sign and median as a horizontal line inside the box. Statistical significance is indicated as follows: *p<0.001 vs CCWB; **p<0.05 vs CL; ***p<0.001vs SE; ****p<0.05 vs CL.</p

How to make brain imaging research efficient and reproducible: building software and standards

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