Class II Transactivator (CIITA) Enhances Cytoplasmic Processing of HIV-1 Pr55Gag

The Pr55(gag) (Gag) polyprotein of HIV serves as a scaffold for virion assembly and is thus essential for progeny virion budding and maturation. Gag localizes to the plasma membrane (PM) and membranes of late endosomes, allowing for release of infectious virus directly from the cell membrane and/or upon exocytosis. The host factors involved in Gag trafficking to these sites are largely unknown. Upon activation, CD4+ T cells, the primary target of HIV infection, express the class II transcriptional activator (CIITA) and therefore the MHC class II isotype, HLA-DR. Similar to Gag, HLA-DR localizes to the PM and at the membranes of endosomes and specialized vesicular MHC class II compartments (MIICs). In HIV producer cells, transient HLA-DR expression induces intracellular Gag accumulation and impairs virus release.Here we demonstrate that both stable and transient expression of CIITA in HIV producer cells does not induce HLA-DR-associated intracellular retention of Gag, but does increase the infectivity of virions. However, neither of these phenomena is due to recapitulation of the class II antigen presentation pathway or CIITA-mediated transcriptional activation of virus genes. Interestingly, we demonstrate that CIITA, apart from its transcriptional effects, acts cytoplasmically to enhance Pr160(gag-pol) (Gag-Pol) levels and thereby the viral protease and Gag processing, accounting for the increased infectivity of virions from CIITA-expressing cells.This study demonstrates that CIITA enhances HIV Gag processing, and provides the first evidence of a novel, post-transcriptional, cytoplasmic function for a well-known transactivator

Patterns and Risk Factors of Helminthiasis and Anemia in a Rural and a Peri-urban Community in Zanzibar, in the Context of Helminth Control Programs

In many parts of the developing world, parasitic worms and anemia are of considerable public health and economic importance. We studied the patterns and risk factors of parasitic worm infections in a rural and a peri-urban community on Zanzibar Island, Tanzania, in the context of national deworming programs. We invited 658 individuals aged between 5 and 100 years and examined their stool and urine for the presence of parasitic worm eggs. Additionally, we obtained a finger-prick blood sample to estimate the level of anemia and to assess for specific immune reactions against parasitic worm infections. We found that, despite large-scale deworming efforts in Zanzibar over the past 15 years, three-quarter of the rural participants and half of the peri-urban residents were infected with parasitic worms. Every second participant was anemic. Risk factors for a parasitic worm infection were age, sex, consumption of raw vegetables or salad, recent travel history, and socio-economic status. For a sustainable control of parasitic worm infections and prevention of anemia, access to safe and efficacious drugs, complemented with health education and improvements in water supply and adequate sanitation are necessary

Fundamental role of C1q in autoimmunity and inflammation

C1q, historically viewed as the initiating component of the classical complement pathway, also exhibits a variety of complement-independent activities in both innate and acquired immunity. Recent studies focusing on C1q\u27s suppressive role in the immune system have provided new insight into how abnormal C1q expression and bioactivity may contribute to autoimmunity. In particular, molecular networks involving C1q interactions with cell surface receptors and other ligands are emerging as mechanisms involved in C1q\u27s modulation of immunity. Here, we discuss the role of C1q in controlling immune cell function, including recently elucidated mechanisms of action, and suggest how these processes are critical for maintaining tissue homeostasis under steady-state conditions and in preventing autoimmunity