Ingestion of the malaria pigment hemozoin renders human macrophages less permissive to HIV-1 infection.

Few studies have investigated the pathophysiologic mechanisms responsible for what seems to be a possible interaction between Plasmodium falciparum, the causative agent of malaria, and HIV-1 in dually infected patients. It has been shown that Plasmodium parasites detoxify heme molecules into a pigment called hemozoin (HZ), which can significantly modulate the immune system. The primary objective of this study was to determine whether exposure of human primary monocyte-derived macrophages (MDMs) to the malaria pigment influences the process of HIV-1 infection. We report here that HIV-1 replication is significantly diminished in HZ-loaded MDMs. The HZ-mediated reduction in virus replication is due to a block at a step in the virus life cycle occurring between the completion of full-length reverse transcripts and integration of viral DNA within the host chromosome. Understanding the pathological mechanisms involved in P. falciparum and HIV-1 co-infection is of high importance because of possible therapeutic ramifications.

Discrimination between exosomes and HIV-1: purification of both vesicles from cell-free supernatants.

Although enveloped retroviruses bud from the cell surface of T lymphocytes, they use the endocytic pathway and the internal membrane of multivesicular bodies for their assembly and release from macrophages and dendritic cells (DCs). Exosomes, physiological nanoparticles produced by hematopoietic cells, egress from this same pathway and are similar to retroviruses in terms of size, density, the molecules they incorporate and their ability to activate immune cells. Retroviruses are therefore likely to contaminate in vitro preparations of exosomes and vice versa and sucrose gradients are inefficient at separating them. However, we have found that their sedimentation velocities in an iodixanol (Optiprep) velocity gradient are sufficiently different to allow separation and purification of both vesicles. Using acetylcholinesterase as an exosome marker, we demonstrate that Optiprep velocity gradients are very efficient in separating exosomes from HIV-1 particles produced on 293T cells, primary CD4(+) T cells, macrophages or DCs, with exosomes collecting at 8.4-12% iodixanol and HIV-1 at 15.6%. We also show that immunodepletion with an anti-acetylcholinesterase antibody rapidly produces highly purified preparations of HIV-1 or exosomes. These findings have applications in fundamental research on exosomes and/or AIDS, as well as in clinical applications where exosomes are involved, more specifically in tumour therapy or in gene therapy using exosomes generated from DCs genetically modified by transfection with virus.

Virus attachment and replication are promoted after acquisition of host CD28 and CD152 by HIV-1.

CD28 is constitutively expressed on CD4(+) cells, but its homologue CD152 is only weakly expressed after cell activation. To determine whether these 2 costimulatory molecules can be inserted into human immunodeficiency virus type 1 (HIV-1), virus was produced in CD28- and CD152-expressing Jurkat-derived cells. Both molecules were efficiently acquired by virions. Virus attachment and infectivity were more affected by CD152 than by CD28. Given that CD28/CD152-CD80/CD86 interactions play a dominant role in antigen presentation, it can thus be proposed that the association between virus-anchored host CD28/CD152 and cell-surface CD80/CD86 on target cells might have consequences for the transmission and pathogenesis of HIV-1.