AEGiS-15IAC: HIV transmission model reveals rapid dissemination of SIV following oral inoculation.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

HIV transmission model reveals rapid dissemination of SIV following oral inoculation.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. ThOrA1441)

Sodora DL, Milush JM, Kosub D, Schmidt K, Scott F, Brown C, Westmoreland S, Marthas M
University of Texas Southwestern Med. Center, Dallas, United States

BACKGROUND: Development of an HIV vaccine capable of preventing mucosal transmission relies on a thorough understanding of the earliest events post-infection. The majority of HIV infections occur via transmission of the virus across a mucosal surface as occurs during oral transmission following both mother-to-child and genital-oral exposure. The goal of this study was to utilize the simian immunodeficiency virus (SIV)/macaque animal model to assess the sites of entry and rate of spread of SIV following a nontraumatic oral administration of virus.

METHODS: Rhesus macaques were orally inoculated with SIVmac251 and necropsied after 1 (n=3), 2 (n=2), 4 (n=3), 7 (n=2), and 14 (n=1) days post-inoculation (dpi). The presence of SIV nucleic acid was assessed utilizing in situ hybridization, quantitative real-time PCR, and nested PCR techniques.

RESULTS: Here assessment of SIV entry following a nontraumatic oral exposure provides evidence that oral and esophageal mucosa, as well as tonsils, represent the most likely viral entry sites. Following entry the spread of virus to regional and peripheral lymph nodes was rapid, observed by 1 dpi. By 4 dpi hundreds and by 7 dpi greater than ten thousand copies of SIV-DNA (per million cell equivalents) could be detected in numerous lymph nodes. Identification of SIV nucleic acid within T cells and macrophages implicates these cell types in the viral spread, although dissemination of free virus likely plays a role as well.

CONCLUSIONS: These studies indicate that viral spread following oral transmission is very rapid, making it difficult for the immune response to eliminate the infection once initiated. Therefore, vaccine strategies capable of preventing infection of the first target cell (i.e. through neutralizing antibodies) might be the most efficacious at blocking mucosal transmission of SIV/HIV.

Keywords: AEGIS, SIV, HIV, Acquired Immunodeficiency Syndrome, HIV Seropositivity, Simian Acquired Immunodeficiency Syndrome, HIV Infections, Macaca mulatta, AIDS Vaccines, Mucous Membrane, Lymph Nodes, Anti-HIV Agents, Animal, Child, Humans, transmission

040711
ThOrA1441