Antibodies that enhance human immunodeficiency virus (HIV) infectivity have been found in the blood of infected individuals and in infected or immunized animals. These findings raise serious concern for the development of a safe vaccine against acquired immunodeficiency syndrome. To address the in vivo relevance and mechanism of this phenomenon, antibody-dependent enhancement of HIV infectivity in peripheral blood macrophages, lymphocytes, and human fibroblastoid cells was studied. Neither Leu3a, a monoclonal antibody directed against the CD4 receptor, nor soluble recombinant CD4 even at high concentrations prevented this enhancement. The addition of monoclonal antibody to the Fc receptor III (anti-FcRIII), but not of antibodies that react with FcRI or FcRII, inhibited HIV type 1 and HIV type 2 enhancement in peripheral blood macrophages. Although enhancement of HIV infection in CD4+ lymphocytes could not be blocked by anti-FcRIII, it was inhibited by the addition of human immunoglobulin G aggregates. The results indicate that the FcRIII receptor on human macrophages and possibly another Fc receptor on human CD4+ lymphocytes mediate antibody-dependent enhancement of HIV infectivity and that this phenomenon proceeds through a mechanism independent of the CD4 protein.
The sera from 16 individuals infected with the human immunodeficiency virus (HIV) at different clinical stages were evaluated for antibody-dependent neutralization and/or enhancement of infectivity by HIV. The HIV isolate from each individual (homotypic) and established laboratory strains showing broad cellular host range and cytopathicity were used. All sera could neutralize one of the laboratory-passaged isolates, whereas only two could neutralize the corresponding homotypic strain. Seven homotypic isolates were enhanced by serum from the respective individual. This activity was primarily observed in patients with acquired immune deficiency syndrome. Moreover, the tropism for macrophages of four of these seven viral isolates was found to be enhanced by the homotypic sera. Finally, sequential pairs of HIV and sera obtained from five HIV-infected individuals with different clinical progression were studied over time. The enhancing activity of three of the five sera appeared to increase over time, indicating changes in both the host virus population and the type of antibodies produced. These results suggest that enhancing antibodies contribute to the spread and pathogenesis of HIV in vivo. They emphasize the necessity of studying further the association of enhancing antibodies and disease progression in infected individuals.
Introduction The COVID-19 pandemic has impacted sleep, with some populations such as essential workers reporting insomnia and poor sleep health. Prior research has suggested (but not tested) that this worsening of sleep may be tied to a lack of control over one’s health or safety during the pandemic. This study tests this prediction and examines the role of perceived control as a protective factor against poor sleep in essential workers. Methods This study uses data from the NDSU National COVID Study, which has followed 301 nationally-representative American adults across four waves of data collection since April 2020. The current analysis includes data from wave 1 (April 2020) in 279 participants who had complete demographic, essential worker, perceived control (including domain general perceived control as well as health, COVID, work-specific control), and sleep health (RU SATED) data. Using t-tests and correlations, we hypothesized: (1) sleep health would be worse in essential workers compared with others; (2) perceived control would relate to better sleep health; and (3) perceived control would be a stronger predictor of sleep health in essential workers relative to others. Results There were no significant differences in sleep health between essential workers (N=44, M=8.27, SD=2.72) and others (N=235, M=8.46, SD=2.54; t=-0.44, p=.66). In the full sample, all indices of perceived control were significantly related to better sleep health (rs=.17-.31, ps<.004). Associations were stronger in essential workers (N=44, rs=.30-.56, ps<.05) than in others (N=235, rs=.13-.31, ps<.04). In sensitivity analyses that excluded participants not working for pay (e.g., people who were unemployed, retired, or receiving disability) from the other category, moderation effects were stronger; only COVID-related perceived control was significantly related to sleep health (N=110; r=.24, p=.01) in non-essential workers. Conclusion This is the first study to demonstrate links between perceived control and sleep. Although sleep health was not significantly different between essential and non-essential workers, we found that perceived control was especially beneficial for essential workers’ sleep. Our results suggest interventions to improve perceived control, a modifiable psychosocial resource, might improve sleep health for essential workers. Support (If Any) L30 HL143741 to KAD from NHLBI; Research and Creative Activity Award to KAD and JMH from NDSU.
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