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Variation in virological parameters and antibody responses in macaques after atraumatic vaginal exposure to a
O Neildez1, R Le Grand, A Chéret
1CEA, Service de Neurovirologie, CRSSA, DSV/DRM, Fontenay aux Roses, France.
Abstract:
We developed an animal model for the male-to-female transmission of human immunodeficiency virus, consisting of an atraumatic vaginal application of simian immunodeficiency virus onto the intact vaginal mucosa of cynomolgus macaques. Different doses of a pathogenic isolate of SIVmac251, with or without seminal plasma, were infused into the vaginas of female macaques. Infection of macaques could be achieved after a single exposure to the virus. Two patterns of infection were underscored with no relation to the virus dose inoculated: in 50% of the monkeys, SIV was persistently recovered and a strong antibody response to SIV was evidenced in blood and vaginal secretions. In the other infected animals, SIV infection was only transiently evidenced and a weak systemic antibody response was detected. It appeared that the presence of seminal plasma may be implicated in this variability only when low doses of virus are inoculated. Sequence analysis of the env gene of SIV revealed that most of the persistently viraemic animals were infected with a viral variant different from that of transiently viraemic macaques.
Insights
Researchers created a new animal model for studying male-to-female human immunodeficiency virus transmission using simian immunodeficiency virus in macaques. This model reveals distinct infection patterns and viral variants, aiding transmission research.
Area of Science:
- Primate models
- Virology
- Infectious diseases
Background:
- Male-to-female transmission of human immunodeficiency virus (HIV) remains a significant global health challenge.
- Understanding the initial stages of viral acquisition is crucial for developing effective prevention strategies.
Purpose of the Study:
- To develop and characterize a novel animal model for male-to-female HIV transmission.
- To investigate the impact of viral dose and seminal plasma on simian immunodeficiency virus (SIV) infection dynamics in female macaques.
Main Methods:
- An atraumatic vaginal application model using simian immunodeficiency virus (SIVmac251) in intact cynomolgus macaque vaginal mucosa.
- Infusion of varying doses of SIV, with and without seminal plasma, into female macaques.
- Monitoring viral recovery, antibody responses, and sequence analysis of the SIV env gene.
Main Results:
- Successful infection achieved after a single SIV exposure.
- Two distinct infection patterns observed: persistent viremia with strong antibody response (50%) and transient viremia with weak antibody response.
- Seminal plasma appeared to influence infection variability primarily at low viral doses.
- Sequence analysis indicated distinct viral variants in persistently versus transiently infected animals.
Conclusions:
- The developed macaque model effectively recapitulates key aspects of male-to-female SIV/HIV transmission.
- Viral dose, seminal plasma, and distinct viral variants contribute to the heterogeneity of initial infection outcomes.
- This model provides a valuable platform for studying transmission dynamics and evaluating interventions.