BackgroundCholesterol pathways play an important role at multiple stages during the HIV-1 infection cycle. Here, we investigated the role of cholesterol trafficking in HIV-1 replication utilizing Niemann-Pick Type C disease (NPCD) cells as a model system.ResultsWe used a unique NPC2-deficient cell line (NPCD55) that exhibited Gag accumulation as well as decreased NPC1 expression after HIV infection. Virus release efficiency from NPCD55 cells was similar to that from control cells. However, we observed a 3 to 4-fold enhancement in the infectivity of virus released from these cells. Fluorescence microscopy revealed accumulation and co-localization of Gag proteins with cholesterol in late endosomal/lysosomal (LE/L) compartments of these cells. Virion-associated cholesterol was 4-fold higher in virions produced in NPCD55 cells relative to virus produced in control cells. Treatment of infected NPCD55 cells with the cholesterol efflux-inducing drug TO-9013171 reduced virus infectivity to control levels.ConclusionsThese results suggest cholesterol trafficking and localization can profoundly affect HIV-1 infectivity by modulating the cholesterol content of the virions.
SUMMARY The temperatures of 587 children were taken before and after diphtheria/tetanus/pertussis (DTP) or diphtheria/tetanus (DT) vaccine. Only slight temperature increases were found but these were notably more frequent after plain than adsorbed DTP vaccine preparations and the frequency increased with each successive dose.The frequent occurrence ofhigh fever after diphtheria/ tetanus/pertussis (DTP) vaccine sometimes associated with febrile convulsions has been reported in the USA.1 2 3 We compared the axillary temperatures of young British children before and after vaccination with either DTP or diphtheria/tetanus (DT) vaccine. Local reactions to each vaccine were also recorded.
Participants and methodsWe studied 587 infants attending local health authority clinics in Dorset for their first, second, or third dose of vaccine in the course of routine primary immunisation. During the study, 401 children had one dose of either DTP or DT vaccine, 151 had two doses, and 35 had a full course of three injections. Temperatures were therefore taken before and after 808 doses of vaccine. All the DT vaccine and most of the DTP vaccine were adsorbed preparations, but for 43 of the DTP doses a plain preparation was used. Each of the vaccines was prepared by the same manufacturer (Wellcome). Temperatures were taken by one of us (E M C), immediately before vaccination at the clinic and then in the infants' homes four hours or 20-24 hours, or both, later. Care was taken to ensure that the thermometer was held firmly in the axilla and remained in place for two minutes. The diameters of any erythema occurring at the site of injectionwere measured with a ruler and the presence and degree of swelling were recorded.
ResultsTemperatures. Only mild temperature increases were found and for the purposes of the study fever was defined as an axillary temperature of 37.5°C or more. Four of the 808 prevaccination temperatures were greater than 37. 5°C and showed no postvaccination increases. These four (five postvaccination temperature readings) have been excluded from the study. Only four of the 283 temperatures (1 %) taken at 4 hours in DTP vaccinated children were more than 37. 5C. The temperature increases were slight and none of the children with fever at 4 hours still had fever at 20-24 hours. These 4 hour fevers all followed adsorbed DTP vaccine. No temperatures greater than 37.5'C were found 4 hours after DT.Fever was more frequent at 20-24 hours after DTP than at 4 hours, was more common after plain than after adsorbed DTP vaccine (Table), but was mild after both preparations (Figure). After adsorbed DT vaccine, fever was infrequent (Table).As might be expected, fever was more frequent when the postvaccination temperature was taken in the afternoon or evening than in the morning. The
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