Herpes simplex virus type-2 stimulates HIV-1 replication in cervical tissues: implications for HIV-1 transmission and efficacy of anti-HIV-1 microbicides.

Herpes Simplex virus Type-2 (HSV-2) increases the risk of HIV-1 acquisition, yet the mechanism for this viral pathogen to regulate the susceptibility of the cervicovaginal mucosa to HIV-1 is virtually unknown. Using ex vivo human ectocervical tissue models, we report greater levels of HIV-1 reverse transcription, DNA integration, RNA expression, and virions release in HIV-1/HSV-2 co-infected tissues compared with HIV-1 only infected tissues (P<0.05). Enhanced HIV-1 replication was associated with increased CD4, CCR5, and CD38 transcription (P<0.05) and increased number of CD4(+)/CCR5(+)/CD38(+) T cells in HIV-1/HSV-2 co-infected tissues compared with tissues infected with HIV-1 alone. Tenofovir (TFV) 1% gel, the leading microbicide candidate, demonstrated only partial protection against HIV-1, when applied vaginally before and after sexual intercourse. It is possible that mucosal inflammation, in particular that induced by HSV-2 infection, may have decreased TFV efficacy. HSV-2 upregulated the number of HIV-1-infected cells and elevated the concentration of TFV needed to decrease HIV-1 infection. Similarly, only high concentrations of TFV inhibited HSV-2 replication in HIV-1/HSV-2-infected tissues. Thus, HSV-2 co-infection and mucosal immune cell activation should be taken into consideration when designing preventative strategies for sexual transmission of HIV-1.

Enhanced HIV-1 replication in ex vivo ectocervical tissues from post-menopausal women correlates with increased inflammatory responses.

Knowledge about early innate immune responses at the mucosal surfaces of the female genital tract is important in understanding the pathogenesis of heterosexual transmission of human immunodeficiency virus type-1 (HIV-1). As estradiol decreases inflammatory responses, we postulated that an estradiol-deficient state such as post-menopause could enhance expression of inflammatory factors that stimulate HIV-1 replication. We compare HIV-1 integration, transcription, and viral p24 release levels among ectocervical tissues obtained from pre- and post-menopausal donors. We detected enhanced HIV-1 p24 release levels in post- compared with pre-menopausal tissues (P<0.0001), but saw no difference in HIV-1 integration. Overall, 100% of post-menopausal tissues exhibited levels of HIV-1 transcription above background compared with only 60% of pre-menopausal tissues. Increased HIV-1 transcription was associated with enhanced interleukin (IL)-1ß, IL-6, monocyte chemotactic protein-1, growth-regulated oncogene-α, and interferon-γ-inducible protein-10 expression. Neutralization and nuclear factor-κB-targeting small-interfering RNA experiments both decreased HIV-1 transcription, suggesting that the early inflammatory response may facilitate HIV-1 replication in ex vivo ectocervical tissues from post-menopausal women.

Type of rectal contents and infectivity of domiciliary populations of Triatoma infestans (Hemiptera: Reduviidae) in Argentina.

Different types of rectal content in domiciliary populations of Triatoma infestans (Hemiptera: Reduviidae: Triatominae) were associated with differences in the degree of infection with Trypanosoma (Schizotrypanum) cruzi. Field studies were carried out in a region of Argentina (Cordoba) where Chagas' disease is endemic. The rectal contents of domiciliary T. infestans were classified by color (clear, yellow, or brown) and the number of infective metacyclic stages of T. cruzi. The seasonal percentage of triatomines with metacyclics did not vary significantly, except in adults, in which it was greatest in spring (November-December). The mean density of T. cruzi per microliter of rectal material varied during the year, according to instar and color of the rectal contents. Clear recta had most metacyclics. December (late spring) may be more important for vectorial transmission of T. cruzi, because there are more infective adults (788) with higher counts of rectal metacyclics.

Are dead Triatoma infestans a competent vector of Trypanosoma cruzi?

After Triatoma infestans death, Trypanosoma cruzi survived several days, maintaining the ability to infect a vertebrate host. Dead bugs from an endemic area collected during an official spraying comapign showed mobile rectal tripanosomes up to 14 days after vector death. Two days after vector death2, 760 tripomastigotes were found alive in its rectal material. However, the number of mobile tripomastigotes decreased significantly from the 5th day after death. Laboratory proofs with third and fifth nymphal stage showed similar results. Living tripanosomes were found in their rectal material at 10 days in third stage and even at 30 days in fifth nymphal stage. The mean number of tripomastigotes had no changes up to 10 days in third nymphal stage and increased significantly from 1 to 10 days in the fifth stage. Conjuctival instillation as well as intraperitoneal innoculation to mice, of metacyclic forms from dead T. infestans produced infection in the vertebrate host. Present results show that human contact with dead vector highly probable in summer and living and infective T. cruzi are available for transmision in the vector

Are dead Triatoma infestans a competent vector of Trypanosoma cruzi?

After Triatoma infestans death, Trypanosoma cruzi survived several days, maintaining the ability to infect a vertebrate host. Dead bugs from an endemic area collected during an official spraying campaign showed mobile rectal trypanosomes up to 14 days after vector death. Two days after vector death 2,760 trypomastigotes were found alive in its rectal material. However, the number of mobile trypomastigotes decreased significantly from the 5th day after death. Laboratory proofs with third and fifth nymphal stage showed similar results. Living trypanosomes were found in their rectal material at 10 days in third stage and even at 30 days in fifth nymphal stage. The mean number of trypomastigotes had no changes up to 10 days in third nymphal stage and increased significantly from 1 to 10 days in the fifth stage. Conjunctival instillation as well as intraperitoneal inoculation to mice, of metacyclic forms from dead T. infestans produced infection in the vertebrate host. Present results show that human contact with dead vector is highly probable in summer and living and infective T. cruzi are available for transmission in the vector.

Seasonal changes in infectivity of domestic populations of Triatoma infestans.

This paper examines the infection rate of Trypanosoma cruzi in Triatoma infestans, the main vector of Chagas disease in Argentina and neighbouring countries. The study was carried out in 1986-1987 on 5 houses (ranchos) in the endemic area of central Argentina. Domestic T. infestans populations were sampled in each season with a constant capture effort (2.5 man-hours/house) using a chemical irritant. The rectal content of the bugs was examined for the presence of T. cruzi. The vector population density showed seasonal changes with highest values during the hot season (November-April). The percentage of infected bugs was higher in mid-spring (November) and autumn (April) than in winter (August) and early spring (October). The mean number of parasites (epimastigotes and trypomastigotes) per microliter of rectal material was very high during mid- and late spring (December). The percentage and number of metacyclic forms differed between seasons, reaching the highest values in late spring. The percentage of infected bugs in houses with children younger than 10 years old was higher than that in houses without children, during all the seasons. Late spring seemed to be the period when domestic populations of T. infestans had the highest vector potential.