Viral dynamics of early HIV infection in neonatal macaques after oral exposure to HIV‐2₂₈₇: an animal model with implications for maternal–neonatal HIV transmission

Abstract

A model of vertical HIV transmission was developed using oral HIV-2(287) exposure of newborn Macaca nemestrina. The minimal Animal Infectious Dose for this oral route was found to be 10-fold higher than that for atraumatic viral transmission across other mucosal membranes (vaginal/rectal) of juvenile macaques. However, once infection was established, viral replication was rapid and plasma viremia could be detected by reverse-transcriptase polymerase chain reaction and viral co-culture within 1 week following exposure. No animal was resistant to infection and all macaques initially exposed to a subinfectious viral inoculum were subsequently infected by re-exposure of mucosal membranes. Higher viral load during primary infection correlated with a more rapid CD4 depletion; however, all HIV-2(287)-infected animals developed CD4 depletion during the observation period. This animal model can now be used to study early viral replication in the presence and absence of anti-retroviral agents to help identify conditions to reduce vertical HIV transmission in human newborns.

Molecular Interactions of Human Immunodeficiency Virus Type 1 with Primary Human Oral Keratinocytes

“…It has been well described for the past decade or more that a variety of salivary inhibitors decrease HIV-1 infectivity in the oral cavity (108,109). Nonetheless, ongoing studies have suggested that oral transmission of the virus remains quite common in a number of important settings in vivo (6,7,51). These enigmatic processes require significant evaluations to dissect, in a prioritized manner, the full virus:host cell interactions which occur in vivo and lead to oral HIV-1 transmission and pathogenesis.…”

Rapid Virus Dissemination in Infant Macaques after Oral Simian Immunodeficiency Virus Exposure in the Presence of Local Innate Immune Responses

“…Assuming that the viral set-point is determined early in infection (15,42), a better understanding of the mechanisms of oral HIV-1 transmission and early virus-host interactions at mucosal entry sites is needed. The infant rhesus macaque model of simian immunodeficiency virus (SIV) infection is extremely valuable in addressing this question and testing intervention strategies (9,14,16,24,37,38,43,44). We have recently developed a physiologically more-relevant SIV infection model in infant macaques that consists of repeated oral SIV exposures by feeding multiple times daily for a fixed time period to mimic HIV-1 infection via breast-feeding in humans (36,40,43,45).…”

Oral epithelial cells and their interactions with HIV‐1

“…Despite this, oral transmission can occur. For example, SIV transmission across non-traumatised oral epithelia, resulting in dissemination and systemic infection in primates, has been reported in several studies (Baba et al, 1996;Joag et al, 1997;Herz et al, 2002;Milush et al, 2004). As a result, the epithelium may represent either a physical barrier against direct infection or a potential reservoir to aid infection.…”