Expression of P. falciparum var Genes Involves Exchange of the Histone Variant H2A.Z at the Promoter

Plasmodium falciparum employs antigenic variation to evade the human immune response by switching the expression of different variant surface antigens encoded by the var gene family. Epigenetic mechanisms including histone modifications and sub-nuclear compartmentalization contribute to transcriptional regulation in the malaria parasite, in particular to control antigenic variation. Another mechanism of epigenetic control is the exchange of canonical histones with alternative variants to generate functionally specialized chromatin domains. Here we demonstrate that the alternative histone PfH2A.Z is associated with the epigenetic regulation of var genes. In many eukaryotic organisms the histone variant H2A.Z mediates an open chromatin structure at promoters and facilitates diverse levels of regulation, including transcriptional activation. Throughout the asexual, intraerythrocytic lifecycle of P. falciparum we found that the P. falciparum ortholog of H2A.Z (PfH2A.Z) colocalizes with histone modifications that are characteristic of transcriptionally-permissive euchromatin, but not with markers of heterochromatin. Consistent with this finding, antibodies to PfH2A.Z co-precipitate the permissive modification H3K4me3. By chromatin-immunoprecipitation we show that PfH2A.Z is enriched in nucleosomes around the transcription start site (TSS) in both transcriptionally active and silent stage-specific genes. In var genes, however, PfH2A.Z is enriched at the TSS only during active transcription in ring stage parasites. Thus, in contrast to other genes, temporal var gene regulation involves histone variant exchange at promoter nucleosomes. Sir2 histone deacetylases are important for var gene silencing and their yeast ortholog antagonises H2A.Z function in subtelomeric yeast genes. In immature P. falciparum parasites lacking Sir2A or Sir2B high var transcription levels correlate with enrichment of PfH2A.Z at the TSS. As Sir2A knock out parasites mature the var genes are silenced, but PfH2A.Z remains enriched at the TSS of var genes; in contrast, PfH2A.Z is lost from the TSS of de-repressed var genes in mature Sir2B knock out parasites. This result indicates that PfH2A.Z occupancy at the active var promoter is antagonized by PfSir2A during the intraerythrocytic life cycle. We conclude that PfH2A.Z contributes to the nucleosome architecture at promoters and is regulated dynamically in active var genes

Partner-Level Factors Associated with Insertive and Receptive Condomless Anal Intercourse Among Transgender Women in Lima, Peru

Condomless anal intercourse among transgender women (TW) in Peru has been shown to vary by the type of partner involved (e.g. primary vs. casual vs. transactional sex partner), but no previous studies have explored variations in partner-level patterns of condom use according to type of anal intercourse. We evaluated the relationship between partnership characteristics and condom use during insertive (IAI) versus receptive anal intercourse (RAI) among TW with recent, non-female partners. Condomless IAI was more common with transactional and casual sex partners and by TW who self-reported HIV-uninfected serostatus (p<0.05), alcohol use disorders, or substance use before sex. Condomless RAI was more common with primary partners and by TW who described their HIV serostatus as unknown (p<0.05). Examining partner-level differences between condomless IAI and RAI reveals distinct patterns of HIV/STI risk among TW, suggesting a need for HIV prevention strategies tailored to the specific contexts of partners, practices, and networks

HIV Status Communication with Sex Partners and Associated Factors Among High-Risk MSM and Transgender Women in Lima, Peru

Men who have sex with men (MSM) and transgender women (TW) are key populations in the HIV epidemic. HIV status communication between sex partners can inform decisions regarding sexual behavior. MSM and TW were asked about HIV status communication with sex partners at baseline, 9- and 18-months. GEE models assessed associations with HIV status communication at baseline using prevalence ratios (PRs) and longitudinally using odds ratios (ORs). At baseline, those who had previously had an HIV test, disclosed their HIV status to 42&nbsp;% of their sex partners. HIV status communication was associated with knowing their sex partner's HIV status at baseline (aPR 5.20) and longitudinally (aOR 1.86). HIV positivity at baseline was negatively associated with HIV status communication during follow-up (aOR 0.55). All reported aPRs and aORs have p&nbsp;&lt;&nbsp;0.05. Interventions promoting HIV status communication and more frequent HIV testing should be explored as current efforts are insufficient