Trypanosoma cruzi (Chagas' disease agent) reduces HIV-1 replication in human placenta.
BACKGROUND
Several factors determine the risk of HIV mother-to-child transmission (MTCT), such as coinfections in placentas from HIV-1 positive mothers with other pathogens. Chagas' disease is one of the most endemic zoonoses in Latin America, caused by the protozoan Trypanosoma cruzi. The purpose of the study was to determine whether T. cruzi modifies HIV infection of the placenta at the tissue or cellular level.


RESULTS
Simple and double infections were carried out on a placental histoculture system (chorionic villi isolated from term placentas from HIV and Chagas negative mothers) and on the choriocarcinoma BeWo cell line. Trypomastigotes of T. cruzi (VD lethal strain), either purified from mouse blood or from Vero cell cultures, 24 h-supernatants of blood and cellular trypomastigotes, and the VSV-G pseudotyped HIV-1 reporter virus were used for the coinfections. Viral transduction was evaluated by quantification of luciferase activity. Coinfection with whole trypomastigotes, either from mouse blood or from cell cultures, decreased viral pseudotype luciferase activity in placental histocultures. Similar results were obtained from BeWo cells. Supernatants of stimulated histocultures were used for the simultaneous determination of 29 cytokines and chemokines with the Luminex technology. In histocultures infected with trypomastigotes, as well as in coinfected tissues, IL-6, IL-8, IP-10 and MCP-1 production was significantly lower than in controls or HIV-1 transducted tissue. A similar decrease was observed in histocultures treated with 24 h-supernatants of blood trypomastigotes, but not in coinfected tissues.


CONCLUSIONS
Our results demonstrated that the presence of an intracellular pathogen, such as T. cruzi, is able to impair HIV-1 transduction in an in vitro system of human placental histoculture. Direct effects of the parasite on cellular structures as well as on cellular/viral proteins essential for HIV-1 replication might influence viral transduction in this model. Nonetheless, additional mechanisms including modulation of cytokines/chemokines at placental level could not be excluded in the inhibition observed. Further experiments need to be conducted in order to elucidate the mechanism(s) involved in this phenomenon. Therefore, coinfection with T. cruzi may have a deleterious effect on HIV-1 transduction and thus could play an important role in viral outcome at the placental level.
Dolcini
Guillermina Laura
GL
National Reference Center for AIDS, Microbiology Department, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina. gdolcini@fmed.uba.ar.
Solana
María Elisa
ME
Andreani
Guadalupe
G
Celentano
Ana María
AM
Parodi
Laura María
LM
Donato
Ana María
AM
Elissondo
Natalia
N
González Cappa
Stella Maris
SM
Giavedoni
Luis David
LD
Martínez Peralta
Liliana
L
D000818:Animals; D002460:Cell Line; D014355:Chagas Disease / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D002824:Chorionic Villi / Q000033:anatomy & histology / Q000378:metabolism / Q000821:virology*; D005260:Female; D015497:HIV-1 / Q000378:metabolism / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D010920:Placenta / Q000276:immunology / Q000821:virology; D014349:Trypanosoma cruzi / Q000502:physiology*; D014779:Virus Replication / Q000187:drug effects