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Intrarectal inoculation of macaques by the simian immunodeficiency virus, SIVmne E11S: CD4+ depletion and AIDS
L Kuller1, R E Benveniste, C C Tsai
1Regional Primate Research Center, University of Washington, Seattle 98195, USA.
Abstract:
Macaca nemestrina and Macaca fascicularis were inoculated with various doses of a single-cell clone of SIVmne-infected HuT 78 cells (E11S) by both the intravenous and intrarectal routes. Animals inoculated intravenously at each dose seroconverted and virus was isolated from peripheral blood mononuclear cells, but only the high-dose intrarectally exposed macaques became viremic and seroconverted. However, some seronegative, virus isolation negative intrarectally inoculated macaques showed evidence of infection and disease.
Insights
Intravenous simian immunodeficiency virus (SIV) inoculation led to infection in all macaques. High-dose intrarectal SIV exposure caused infection in some macaques, while others showed disease despite negative tests.
Area of Science:
- Veterinary Virology
- Primate Immunology
- Infectious Disease Modeling
Background:
- Simian immunodeficiency virus (SIV) infection in non-human primates serves as a crucial model for understanding human immunodeficiency virus (HIV) pathogenesis.
- Understanding SIV transmission routes and dose-dependency is vital for developing effective vaccines and interventions.
- Previous studies have explored various SIV strains and inoculation methods, but specific dose-response relationships require further elucidation.
Purpose of the Study:
- To investigate the infectivity and disease progression of SIVmne in Macaca nemestrina and Macaca fascicularis following intravenous and intrarectal inoculation.
- To determine the influence of SIVmne dose on seroconversion, viremia, and viral shedding via different routes.
- To identify potential discrepancies between serological/virological markers and actual infection/disease in intrarectally inoculated macaques.
Main Methods:
- Two macaque species, Macaca nemestrina and Macaca fascicularis, were inoculated with varying doses of a single-cell clone of SIVmne (E11S).
- Inoculations were administered via both intravenous (IV) and intrarectal (IR) routes.
- Animals were monitored for seroconversion, viral isolation from peripheral blood mononuclear cells (PBMCs), and evidence of infection and disease.
Main Results:
- All macaques inoculated intravenously (IV) seroconverted, and SIVmne was isolated from their PBMCs, irrespective of dose.
- Only macaques receiving a high dose of SIVmne intrarectally (IR) became viremic and seroconverted.
- A subset of IR-inoculated macaques that were seronegative and from which virus could not be isolated still exhibited signs of infection and disease.
Conclusions:
- Intravenous inoculation of SIVmne is highly efficient, leading to infection in all animals regardless of dose.
- Intrarectal SIVmne transmission is dose-dependent, with high doses required for consistent viremia and seroconversion.
- The study highlights the potential for subclinical or atypical SIV infection in macaques, underscoring the complexity of disease detection and the need for comprehensive diagnostic approaches.