Early Sites of Virus Replication After Oral SIVmac251 Infection of Infant Macaques: Implications for Pathogenesis
Angela M Amedee1, Bonnie Phillips2, Kara Jensen2
11 Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center , New Orleans, Louisiana.
Insights
Despite preventative measures, 400 infants contract HIV daily, primarily through breastfeeding. This study identifies oral and intestinal tissues as key entry sites for simian immunodeficiency virus (SIV) in infant macaques.
Area of Science:
- Virology
- Immunology
- Pediatric Infectious Diseases
Background:
- Vertical HIV-1 transmission remains a significant global health issue, with breastfeeding being a major transmission route.
- The precise sites of viral entry following oral exposure in infants are not well-defined, hindering targeted prevention strategies.
Purpose of the Study:
- To investigate the early sites of simian immunodeficiency virus (SIV) replication and dissemination in infant macaques following oral exposure.
- To characterize the viral genetic material and cellular tropism in various tissues within the initial hours post-exposure.
Main Methods:
- Quantification of SIV RNA and DNA in oral, intestinal, and systemic tissues of infant macaques within 48-96 hours post-oral SIVmac251 exposure.
- Identification of transmitted founder viruses and cellular tropism using in situ hybridization and CD3+ T cell markers.
Main Results:
- SIV DNA was detected as early as 48 hours, with RNA appearing later (72-96 hours).
- Oral-associated lymph nodes and the ileum showed the highest frequency of SIV RNA and DNA.
- SIV-infected cells in lymph nodes were primarily CD3+ T cells; SIV was also detected in lungs and the cerebrum.
Conclusions:
- The oral cavity and gastrointestinal tract are critical sites for early SIV infection in infants.
- Early detection of SIV in the lungs and brain underscores the urgency of prompt treatment for pediatric HIV to prevent systemic damage.
Abstract:
Despite optimization of preventative measures for vertical HIV-1 transmission, daily, roughly 400 infants become HIV infected, most of them through breastfeeding. Viral entry has been presumed to occur in the gastrointestinal tract; however, the exact entry site(s) have not been defined. Therefore, we quantified simian immunodeficiency virus (SIV) RNA and DNA in oral, intestinal, and systemic tissues of 15 infant macaques within 48-96 h after oral SIVmac251 exposure. SIV DNA was detected as early as 48 h, whereas SIV RNA was typically detected at later time points (72-96 h). Transmitted founder viruses were identical or very similar to a single genotype in the SIVmac251 challenge stock. SIV RNA and DNA were most frequently found in lymph nodes (LNs) draining the oral cavity and in the ileum. Using in situ hybridization, SIV-infected cells in LNs were exclusively represented by CD3+ T cells. SIV RNA and DNA were also detected in the lungs of 20% of the animals, and 60% of the animals had detectable SIV DNA in the cerebrum. The early detection of viral RNA or DNA in lung and brain tissues emphasizes the need for early treatment of pediatric HIV infection to prevent damage not only to the immune system but also to the respiratory tract and central nervous system.
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