title: Inhibition of HIV-1 replication in human monocyte-derived macrophages by parasite Trypanosoma cruzi.
abstract: BACKGROUND
  Cells of monocyte/macrophage lineage are one of the major targets of HIV-1 infection and serve as reservoirs for viral persistence in vivo. These cells are also the target of the protozoa Trypanosoma cruzi, the causative agent of Chagas disease, being one of the most important endemic protozoonoses in Latin America. It has been demonstrated in vitro that co-infection with other pathogens can modulate HIV replication. However, no studies at cellular level have suggested an interaction between T. cruzi and HIV-1 to date.
  
  
  RESULTS
  By using a fully replicative wild-type virus, our study showed that T. cruzi inhibits HIV-1 antigen production by nearly 100% (p<0.001) in monocyte-derived macrophages (MDM). In different infection schemes with luciferase-reporter VSV-G or BaL pseudotyped HIV-1 and trypomastigotes, T. cruzi induced a significant reduction of luciferase level for both pseudotypes in all the infection schemes (p<0.001), T. cruzi-HIV (>99%) being stronger than HIV-T. cruzi (approximately 90% for BaL and approximately 85% for VSV-G) infection. In MDM with established HIV-1 infection, T. cruzi significantly inhibited luciferate activity (p<0.01). By quantifying R-U5 and U5-gag transcripts by real time PCR, our study showed the expression of both transcripts significantly diminished in the presence of trypomastigotes (p<0.05). Thus, T. cruzi inhibits viral post-integration steps, early post-entry steps and entry into MDM. Trypomastigotes also caused a approximately 60-70% decrease of surface CCR5 expression on MDM. Multiplication of T. cruzi inside the MDM does not seem to be required for inhibiting HIV-1 replication since soluble factors secreted by trypomastigotes have shown similar effects. Moreover, the major parasite antigen cruzipain, which is secreted by the trypomastigote form, was able to inhibit viral production in MDM over 90% (p<0.01).
  
  
  CONCLUSIONS
  Our study showed that T. cruzi inhibits HIV-1 replication at several replication stages in macrophages, a major cell target for both pathogens.
authors.affiliation: National Reference Center for AIDS, Microbiology Department, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Andreani
authors.forename: Ana M
authors.initials: AM
authors.lastname: Celentano
authors.forename: María E
authors.initials: ME
authors.lastname: Solana
authors.forename: Silvia I
authors.initials: SI
authors.lastname: Cazorla
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Malchiodi
authors.forename: Liliana A
authors.initials: LA
authors.lastname: Martínez Peralta
authors.forename: Guillermina L
authors.initials: GL
authors.lastname: Dolcini
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000469:parasitology* / Q000821:virology*; D051379:Mice; D009000:Monocytes / Q000166:cytology*; D009928:Organ Specificity; D010271:Parasites / Q000276:immunology / Q000502:physiology*; D015800:Protozoan Proteins; D019713:Receptors, CCR5 / Q000378:metabolism; D012995:Solubility; D014349:Trypanosoma cruzi / Q000276:immunology / Q000502:physiology*; D019065:Virus Assembly / Q000502:physiology; D016662:Virus Integration / Q000502:physiology; D053586:Virus Internalization; D014779:Virus Replication / Q000502:physiology*
chemical_list: D000953:Antigens, Protozoan; D015704:CD4 Antigens; D015800:Protozoan Proteins; D019713:Receptors, CCR5; D003546:Cysteine Endopeptidases; C063214:cruzipain