The type I interferon-inducible factor tetherin retains virus particles on the surfaces of cells infected with vpu-deficient human immunodeficiency virus type 1 (HIV-1). While this mechanism inhibits cell-free viral spread, the immunological implications of tethered virus have not been investigated. We found that surface tetherin expression increased the antibody opsonization of vpudeficient HIV-infected cells. The absence of Vpu also stimulated NK cell-activating Fc␥RIIIa signaling and enhanced NK cell degranulation and NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC). The deletion of vpu in HIV-1-infected primary CD4؉ T cells enhanced the levels of antibody binding and Fc receptor signaling mediated by HIV-positive-patient-derived antibodies. The magnitudes of antibody binding and Fc signaling were both highly correlated to the levels of tetherin on the surfaces of infected primary CD4 T cells. The affinity of antibody binding to Fc␥RIIIa was also found to be critical in mediating efficient Fc activation. These studies implicate Vpu antagonism of tetherin as an ADCC evasion mechanism that prevents antibody-mediated clearance of virally infected cells. IMPORTANCEThe ability of the HIV-1 accessory factor to antagonize tetherin has been considered to primarily function by limiting the spread of virus by preventing the release of cell-free virus. This study supports the hypothesis that a major function of Vpu is to decrease the recognition of infected cells by anti-HIV antibodies at the cell surface, thereby reducing recognition by antibody-dependent clearance by natural killer cells.

BackgroundMore than two-thirds of the world's HIV-positive individuals live in sub-Saharan Africa, where genetic susceptibility to kidney disease is high and resources for kidney disease screening and antiretroviral therapy (ART) toxicity monitoring are limited. Equations to estimate glomerular filtration rate (GFR) from serum creatinine were derived in Western populations and may be less accurate in this population.MethodsWe compared results from published GFR estimating equations with a direct measure of GFR by iohexol clearance in 99 HIV-infected, ART-naïve Kenyan adults. Iohexol concentration was measured from dried blood spots on filter paper. The bias ratio (mean of the ratio of estimated to measured GFR) and accuracy (percentage of estimates within 30% of the measured GFR) were calculated.ResultsThe median age was 35 years, and 60% were women. The majority had asymptomatic HIV, with median CD4+ cell count of 355 cells/mm3. Median measured GFR was 115 mL/min/1.73 m2. Overall accuracy was highest for the Chronic Kidney Disease Epidemiology Consortium (CKD-EPI) equation. Consistent with a prior report, bias and accuracy were improved by eliminating the coefficient for black race (85% of estimates within 30% of measured GFR). Accuracy of all equations was poor in participants with GFR 60–90 mL/min/1.73 m2 (<65% of estimates within 30% of measured GFR), although this subgroup was too small to reach definitive conclusions.ConclusionsOverall accuracy was highest for the CKD-EPI equation. Eliminating the coefficient for race further improved performance. Future studies are needed to determine the most accurate GFR estimate for use in individuals with GFR <90 mL/min/1.73 m2, in whom accurate estimation of kidney function is important to guide drug dosing. Direct measurement of GFR by iohexol clearance using a filter paper based assay is feasible for research purposes in resource-limited settings, and could be used to develop more accurate GFR estimates in African populations.

HIV-1 viremic controllers (VC) spontaneously control infection without antiretroviral treatment. Several studies indicate that IgG Abs from VCs induce enhanced responses from immune effector cells. Since signaling through Fc-γ receptors (FCGRs) modulate these Ab-driven responses, here we examine if enhanced FCGR activation is a common feature of IgG from VCs. Using an infected cell-based system, we observed that VC IgG stimulated greater FCGR2A and FCGR3A activation as compared with noncontrollers, independent of the magnitude of HIV-specific Ab binding or virus neutralization activities. Multivariate regression analysis showed that enhanced FCGR signaling was a significant predictor of VC status as compared with chronically infected patients (CIP) on highly active antiretroviral therapy (HAART). Unsupervised hierarchical clustering of patient IgG functions primarily grouped VC IgG profiles by enhanced FCGR2A, FCGR3A, or dual signaling activity. Our findings demonstrate that enhanced FCGR signaling is a common and significant predictive feature of VC IgG, with VCs displaying a distinct spectrum of FCGR activation profiles. Thus, profiling FCGR activation may provide a useful method for screening and distinguishing protective anti-HIV IgG responses in HIV-infected patients and in monitoring HIV vaccination regimens.

Estimation of amniotic fluid volume is an important part of routine obstetric sonography. A relationship between polyhydramnios and poor perinatal outcome has been reported. This study correlates the severity of polyhydramnios .with perinatal morbidity and mortality. Among 67 cases of polyhydramnios detected in singleton pregnancies, 8 were associated with maternal conditions including noninsulin-dependent diabetes (5 cases), insulin-dependent diabetes (1 case) and gestational diabetes (2 cases). Forty-four were associated with fetal conditions, including fetal anomalies (31 cases), fetal chromosomal disorders (10 cases) and fetal functional disorders (3 cases). Fifteen of the 67 cases had no apparent underlying fetal or maternal cause. Perinatal death occurred in 19 cases (28%) and was associated with fetal anomalies (12 cases), chromosome disorders (6 cases) and a functional fetal abnormality (1 case). Severe polyhydramnios with amniotic pocket dimensions ? 120 mm (91%) or with a need for amniocentesis (91%) were associated with fetal abnormalities in most cases. The rate of perinatal death was not increased, indicating that severe polyhydramnios does not always result in lethal abnormalities.

Umbilical artery blood velocity waveforms were recorded by a pulsed Doppler system in the third trimester of pregnancy in 16 diabetic women (12 class B, 1 class C, 3 class D) and the waveforms were analysed for resistance index (RI = peak systolic velocity minus end diastolic velocity/peak systolic velocity). There was no significant correlation between the RI values and either serum glucose (r = 0.385) or fructosamine levels (r = 0.380). However, the RI values were raised in two cases with serum glucose levels of over 300 mg/dl. With a fall in serum glucose levels, the RI values returned to the normal range. No abnormal umbilical artery velocity waveforms were found when the serum glucose level was below 200 mg/dl.