You can spend your life dying or you can spend your life living : identity transition in people who are HIV-positive

This article examines, through the lenses of HIV-positive people, the unique phenomenon of identity transition. This research proposes that life-changing illnesses, such as HIV, are an undesired 'possession' that people accept to varying degrees, which we refer to as 'ownership'. While illnesses, such as HIV compel individuals to undergo a transformation process that usually begins with a deep feeling of detachment, and then proceeds to acceptance of their illness, and to feeling empowered and in control of their HIV status and lives, this process is very complex and non-linear as it involves many iterative progressions in identity transition. These transitions are highly individualistic; however, the underlying theme is that the more positive trajectories were those of people who focus on their new lives, living with HIV (i.e. taking ownership of their illness), rather than focusing on what they have lost when they became HIV-positive. The findings demonstrate that identity transition is a result of the ways that individuals rework, negotiate and transform their roles, actions and behaviours through their active engagement with support mechanisms. This study suggests that it is vital to promote positive interactions with support mechanisms to ensure that those with HIV view themselves positively.

Churches, mosques, and condoms : understanding successful HIV and AIDS interventions by faith-based organisations

There are an estimated 33 million people living with the Human Immunodeficiency Virus (HIV) worldwide. While national education campaigns have been successful in providing a broad platform of awareness of HIV and AIDS, within some countries faith-based organisations (FBOs) have assumed an important role in educating and supporting local communities to reduce HIV transmission. This article conceptualises the successful characteristics of a Christian organisation in West Papua and a Muslim organisation in Thailand. The ability of both these FBOs to engage successfully with their communities on issues of sexual practice provides important lessons for other FBOs seeking to reduce HIV transmission.

Effect of insulin-like growth factor I on HIV type 1 long terminal repeat-driven chloramphenicol acetyltransferase expression

In this study, we have investigated the ability of insulin-like growth factor I (IGF-I) to inhibit HIV long terminal repeat (LTR)-driven gene expression. Using COS 7 cells cotransfected with tat and an HIV LTR linked to a chloramphenicol acetyltransferase (CAT) reporter, we observed that physiological levels of IGF-I (10-9 M) significantly inhibited CAT expression in a concentration- and time-dependent manner. IGF-I did not inhibit C AT expression in COS 7 cells transfected with pSVCAT, and did not affect CAT expression in the absence of cotransfection with tat . Transfection of HIV-1 proviral DNA into COS 7 cells +/- IGF-I resulted in a significant decrease ( p 0.05) in infectious virion production. Both IGF-I and Ro24-7429 inhibited LTR-driven C AT expression, while TNF- alpha -enhanced CAT expression was not affected by IGF-I. On the other hand, a plasmid encoding parathyroid hormone-related peptide exhibited dramatic additivity of inhibition of CAT expression in COS 7 cells. Finally, we show that in Jurkat or U937 cells cotransfected with HIVLTRCAT/tat, IGF-I significantly inhibited CAT expression. Further, interleukin 4 showed in U937 cells inhibition of CAT expression that was not additive to IGF-I induced inhibition. Our data demonstrate that IGF-I can specifically inhibit HIVLTRCAT expression. This inhibition may occur at the level of the tat /TAR interaction. Finally, this IGF-I effect is seen in target cell lines and similar paths of inhibition may be involved in the various cell types employed.

HIV infection of dendritic cells subverts the IFN induction pathway via IRF-1 and inhibits type 1 IFN production

Many viruses have developed mechanisms to evade the IFN response. Here, HIV-1 was shown to induce a distinct subset of IFN-stimulated genes (ISGs) in monocyte-derived dendritic cells (DCs), without detectable type I or II IFN. These ISGs all contained an IFN regulatory factor 1 (IRF-1) binding site in their promoters, and their expression was shown to be driven by IRF-1, indicating this subset was induced directly by viral infection by IRF-1. IRF-1 and -7 protein expression was enriched in HIV p24 antigen-positive DCs. A HIV deletion mutant with the IRF-1 binding site deleted from the long terminal repeat showed reduced growth kinetics. Early and persistent induction of IRF-1 was coupled with sequential transient up-regulation of its 2 inhibitors, IRF-8, followed by IRF-2, suggesting a mechanism for IFN inhibition. HIV-1 mutants with Vpr deleted induced IFN, showing that Vpr is inhibitory. However, HIV IFN inhibition was mediated by failure of IRF-3 activation rather than by its degradation, as in T cells. In contrast, herpes simplex virus type 2 markedly induced IFNβ and a broader range of ISGs to higher levels, supporting the hypothesis that HIV-1 specifically manipulates the induction of IFN and ISGs to enhance its noncytopathic replication in DCs.

Alteration of the proline at position 7 of the HIV-1 spacer peptide p1 suppresses viral infectivity in a strain dependent manner

The HIV-1 spacer peptide p1 is located in the C-terminus of the Gag polyprotein and separates the nucleocapsid (NC) and p6(Gag). Research centered on p1 has been limited and as yet no function has been ascribed to this spacer peptide. We have previously found that the conserved p1 proline residues (position 7 and 13) are critical for replication in the HIV-1 strain HXB2-BH10. In this study we have focused on the proline rich p1-p6(Gag) C-terminus of HIV-1. We individually examined the role of p1 proline's in multiple strains of HIV-1 and investigated the role of three proline residues in p6(Gag) (P24, P25 and P30). Assessment of the HXB2-BH10 based mutants revealed that Gag-Pol incorporation relative to Gag decreased in the p1 mutant virions, with the double proline mutant the most impaired. Mutating both p1 proline residues was found to abolish infectivity in multiple strains of HIV-1. Independent mutation of the p1 proline at position 7 resulted in a strain-dependent suppression of viral infectivity. This defect correlates with the presence of a tyrosine residue at position 9 of p1 and occurs in the early phase of the HIV-1 replication cycle. The p1 proline residues were found to be functionally distinct from P24, P25 and P30 in p6(Gag). This work affords novel insights into our understanding of the role of p1 in HIV-1 replication.

The packaging and maturation of the HIV-1 Pol proteins

The Pol protein of human immunodeficiency virus type 1 (HIV-1) harbours the viral enzymes critical for viral replication; protease (PR), reverse transcriptase (RT), and integrase (IN). PR, RT and IN are not functional in their monomeric forms and must come together as either dimers (PR), heterodimers (RT) or tetramers (IN) to be catalytically active. Our knowledge of the tertiary structures of the functional enzymes is well advanced, and substantial progress has recently been made towards understanding the precise steps leading from Pol protein synthesis through viral assembly to the release of active viral enzymes. This review will summarise our current understanding of how the Pol proteins, which are initially expressed as a Gag-Pol fusion product, are packaged into the assembling virion and discuss the maturation process that results in the release of the viral enzymes in their active forms. Our discussion will focus on the relationship between structure and function for each of the viral enzymes. This review will also provide an overview of the current status of inhibitors against the HIV-1 Pol proteins. Effective inhibitors of PR and RT are well established and we will discuss the next generation inhibitors of these enzymes as well recent investigations that have highlighted the potential of IN and RNase H as antiretroviral targets.