California HIV/AIDS Research Program

This project compared two HIV testing protocols, an HIV test alone or as part of a bundled package with other tests, to examine which resulted in a higher test uptake in a sample of 725 Latino day laborers. The testing uptake was 29.1% for the HIV-only protocol and 13.6% for the HIV-bundled protocol (p < 0.001). Thus higher levels of testing among day laborers may occur when the HIV test is offered alone. However, no HIV-positive tests were found and few risk behaviors reported. This would argue against the need for routine HIV screening with this population as a whole. HIV testing among Latino day laborers should target those involved in actual high HIV risk behaviors, such as unprotected sex with men or injection drug use.

Not available.  Manuscript unpublished.

HIV Nef acts as an anti-autophagic maturation factor through interaction with beclin-1 (BECN1). We report that exposure of macrophages to infectious or non-infectious purified HIV induces toll-like receptor 8 (TLR8) and BECN1 dependent dephosphorylation and nuclear translocation of TFEB and that this correlates with an increase in autophagy markers. RNA interference for ATG13, TFEB, TLR8, or BECN1 inhibits this HIV-induced autophagy. However, once HIV establishes a productive infection, TFEB phosphorylation and cytoplasmic sequestration are increased resulting in decreased autophagy markers. Moreover, by 7 d post-infection, autophagy levels are similar to mock infected controls. Conversely, although Nef deleted HIV similarly induces TFEB dephosphorylation and nuclear localization, and increases autophagy, these levels remain elevated during continued productive infection. Thus, the interaction between HIV and TLR8 serves as a signal for autophagy induction that is dependent upon the dephosphorylation and nuclear translocation of TFEB. During permissive infection, Nef binds BECN1 resulting in mammalian target of rapamycin (MTOR) activation, TFEB phosphorylation and cytosolic sequestration, and the inhibition of autophagy. To our knowledge, this is the first report of a virus modulating TFEB localization and helps to explain how HIV modulates autophagy to promote its own replication and cell survival.

Latino day laborers endure many hardships as they struggle to adjust as an immigrant community in the United States. This study sought to identify the extent of chronic stress reported by day laborers and the factors associated with stress. 725 Latino day laborers were interviewed. The most reported sources of stress were having immigration-related problems, not having enough money to cover basic needs, having no savings and having work hours change for the worse. Higher chronic stress was associated with homelessness (p < .001) and HIV-related risk behaviors in the previous twelve months (p < .05). In addition, chronic stress was found to be higher among respondents reporting incomes of $5,000 to $10,000 (p = 0.007) and still higher among respondents reporting incomes greater than $10,000 (p < 0.001) compared to those in the lowest income level. Lower chronic stress was associated with having a partner (p < .05) or being single (p = .001) compared to being married. Addressing the stress experienced by day laborers is necessary to prevent potential negative health and mental health consequences among this population.

© 2015 Campbell et al. HIV Nef acts as an anti-autophagic maturation factor through interaction with beclin-1 (BECN1). We report that exposure of macrophages to infectious or non-infectious purified HIV induces toll-like receptor 8 (TLR8) and BECN1 dependent dephosphorylation and nuclear translocation of TFEB and that this correlates with an increase in autophagy markers. RNA interference for ATG13, TFEB, TLR8, or BECN1 inhibits this HIV-induced autophagy. However, once HIV establishes a productive infection, TFEB phosphorylation and cytoplasmic sequestration are increased resulting in decreased autophagy markers. Moreover, by 7 d post-infection, autophagy levels are similar to mock infected controls. Conversely, although Nef deleted HIV similarly induces TFEB dephosphorylation and nuclear localization, and increases autophagy, these levels remain elevated during continued productive infection. Thus, the interaction between HIV and TLR8 serves as a signal for autophagy induction that is dependent upon the dephosphorylation and nuclear translocation of TFEB. During permissive infection, Nef binds BECN1 resulting in mammalian target of rapamycin (MTOR) activation, TFEB phosphorylation and cytosolic sequestration, and the inhibition of autophagy. To our knowledge, this is the first report of a virus modulating TFEB localization and helps to explain how HIV modulates autophagy to promote its own replication and cell survival.