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AIDS Res Hum Retroviruses. 2018 Mar;34(3):286-299. doi: 10.1089/AID.2017.0169. Epub 2018 Jan 17.

Early Sites of Virus Replication After Oral SIVmac251 Infection of Infant Macaques: Implications for Pathogenesis.

Author information

1
1 Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center , New Orleans, Louisiana.
2
2 Department of Microbiology and Immunology and Center for AIDS Research, School of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina.
3
3 Howard University , Washington, District of Columbia.
4
4 AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc. , Frederick National Laboratory for Cancer Research, Frederick, Maryland.
5
5 California National Primate Research Center, University of California , Davis, Davis, California.

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.

KEYWORDS:

infant rhesus macaques; oral SIV infection; tissue distribution; virus replication

PMID:
29237287
PMCID:
PMC5863100
DOI:
10.1089/AID.2017.0169

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