Rapid dissemination of SIV following oral inoculation
Jeffrey M Milush1, David Kosub, Marta Marthas
1Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9113, USA.
Objective:
To assess the earliest events regarding transmission and dissemination of SIV following nontraumatic oral inoculation in macaques.
Design:
Juvenile and neonate rhesus macaques were orally inoculated with SIVmac251 and necropsied at 1, 2, 4, 7, or 14 days post-inoculation. Sites of transmission and the extent of viral spread were assessed by using molecular techniques and in situ hybridization to identify SIV nucleic acid in lymphoid and nonlymphoid tissues.
Results:
This study demonstrates that 1 day post-exposure, SIV nucleic acid was detected in the alimentary canal only in tissues proximal to the stomach, including the oral and esophageal mucosa as well as the tonsils. Following infection, virus was observed to spread rapidly to regional and peripheral lymph nodes by 1 and 2 days post-inoculation (dpi). Hundreds of copies of SIV-DNA were detected 4 dpi, increasing to > 10 000 copies/1 x 10(6) cells by 7 dpi. Identification of SIV positive T cells and macrophages implicates these cell types in viral spread, although dissemination of free virus is also likely.
Conclusions:
Here the oral and esophageal mucosa, as well as tonsils, are demonstrated to be potential sites for viral infection upon nontraumatic oral exposure to SIV in macaques. The rapid dissemination following oral transmission observed in this study is reflective of SIV transmission across other mucosal surfaces. The rapidity with which SIV, and probably HIV, spreads throughout the lymphatics indicates a major obstacle for a vaccine amnestic immune response to eliminate infected cells prior to dissemination.
Insights
Oral inoculation of macaques with SIVmac251 shows rapid viral spread to lymph nodes within 1-2 days. The oral and esophageal mucosa, and tonsils are identified as initial sites of infection, highlighting challenges for vaccine development.
Area of Science:
- Virology
- Immunology
- Primatology
Background:
- Simian immunodeficiency virus (SIV) infection in macaques serves as a model for understanding human immunodeficiency virus (HIV) pathogenesis.
- Oral mucosal transmission is a significant route for various viral infections, yet the early events of SIV oral transmission remain incompletely understood.
Purpose of the Study:
- To investigate the initial sites of SIV transmission and subsequent dissemination following non-traumatic oral inoculation in a macaque model.
- To characterize the temporal dynamics of viral spread in lymphoid and non-lymphoid tissues.
Main Methods:
- Rhesus macaques (juvenile and neonate) were orally inoculated with SIVmac251.
- Tissues were collected at multiple time points (1, 2, 4, 7, and 14 days post-inoculation) for analysis.
- Molecular techniques, including in situ hybridization, were employed to detect SIV nucleic acid and identify infected cells.
Main Results:
- SIV nucleic acid was detected in the oral mucosa, esophagus, and tonsils as early as 1 day post-exposure.
- Rapid viral dissemination to regional and peripheral lymph nodes occurred by 1-2 days post-inoculation.
- Viral load increased significantly by 7 days post-inoculation, with T cells and macrophages identified as key infected cell types.
Conclusions:
- The oral and esophageal mucosa, along with tonsils, are identified as primary sites for SIV infection following oral exposure.
- The rapid dissemination of SIV through the lymphatic system presents a significant challenge for developing effective vaccines, particularly those relying on an amnestic immune response.
