Toxoplasma gondii inhibits R5 HIV-1 replication in human lymphoid tissues ex vivo.
Critical events of HIV-1 pathogenesis occur in lymphoid tissues where HIV-1 is typically accompanied by infections with other pathogens (HIV co-pathogens). Co-pathogens greatly affect the clinical course of the disease and the transmission of HIV. The apicomplexan parasite Toxoplasma gondii is a common HIV co-pathogen associated with AIDS development. Here, we examined the interaction of T. gondii and HIV in coinfected human lymphoid tissue ex vivo. Both pathogens readily replicate in ex vivo infected blocks of human tonsillar tissue. Surprisingly, we found that live T. gondii preferentially inhibits R5 HIV-1 replication in coinfected tissues. This effect is reproduced by treatment of the tissue blocks with recombinant C-18, a T. gondii-encoded cyclophilin that binds to CCR5. These ex vivo findings raise the possibility that, in addition to being a co-factor in HIV disease, T. gondii may influence the outcome of viral infection by preferentially suppressing R5 variants.
Sassi
Atfa
A
Section of Intercellular Interactions, Program of Physical Biology, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
Brichacek
Beda
B
Hieny
Sara
S
Yarovinsky
Felix
F
Golding
Hana
H
Grivel
Jean-Charles
JC
Sher
Alan
A
Margolis
Leonid
L
D000818:Animals; D021983:Cyclophilins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015658:HIV Infections / Q000150:complications / Q000821:virology; D015497:HIV-1 / Q000378:metabolism / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008221:Lymphoid Tissue / Q000469:parasitology / Q000821:virology; D014066:Palatine Tonsil / Q000469:parasitology / Q000821:virology; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D019713:Receptors, CCR5 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D014122:Toxoplasma / Q000145:classification / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology; D014123:Toxoplasmosis / Q000150:complications / Q000821:virology; D014779:Virus Replication / Q000187:drug effects*
D015800:Protozoan Proteins; D019713:Receptors, CCR5; D011994:Recombinant Proteins; D021983:Cyclophilins