Background: In developing nations, there is a substantial risk of HIV-infected woman transmitting the virus to her infant via breast-feeding. Here we utilize a breast-feeding model in macaques to study the spread of simian immunodeficiency virus (SIV) post oral inoculation.

Methods: To mimic breast-feeding, the uncloned swarm SIVmac251 was given orally (2 doses of 1x10⁵ TCID₅₀) to juvenile (n = 8) or neonate (n = 3) rhesus. Macaques were necropsied at 1, 2, 4, 7, and 14 days post-inoculation (dpi). Two (2) rounds of PCR with nested primers that amplify a 597bp fragment of the gag gene were utilized to detect SIV in 25–30 different tissues.

Results: We concluded from initial studies that by 7 (n = 2) and 14 (n = 1) dpi the virus had spread systemically. Additional studies at earlier time points revealed that 88% of neonate (n = 1) tissues and 74% of juvenile (n = 2) tissues were SIV+ as early as 4 dpi. By 2 dpi, 66% of juvenile (n = 2) tissues were SIV+; these tissues were concentrated in the head/neck region (e.g., gingiva, esophagus, submandibular lymph node), but also included lymph nodes in the chest and abdomen. Interestingly in the 25–30 tissues examined after just 1 dpi 30% of the juvenile (n = 1) and 39% of the neonate (n = 2) tissues were SIV+ with the majority of infected tissues located within the head/neck including gingiva, esophagus, brain, and submandibular lymph nodes. SIVnef immunohistochemistry and SIV riboprobe in situ hybridization used in selected tissues confirmed the presence of virally-infected cells. Heteroduplex mobility analysis of SIV+ tissues indicated several viral variants infected each macaque.

Conclusions: Systemic infection, defined as SIV-DNA within a majority of the lymphatic tissues examined, occurred as early as 2 dpi. In addition, the rapid spread of SIV to diverse tissue types by one dpi was particularly dramatic. This rapid dissemination of virus following oral inoculation illustrates one mechanism by which the virus evades the host immune response and establishes its infection. Therefore, any treatment designed to inhibit viral spread after oral transmission would need to be administered within 24 hours post exposure.