In a more recent study, ADCC responses can

induce epitope-specific escape mutations as early as 50 days after T0.[26] Taken together, these studies suggest that the first functional antibody responses to Env appear almost click here concomitantly with binding antibodies, which is approximately 50 days before the emergence of the first detectable neutralizing antibodies against autologous viruses. It goes without saying that antibodies must be present at the time of acquisition to block it and this can only be accomplished by active or passive immunization. In recent years, a good picture of the early events during acquisition after vaginal exposure has emerged (reviewed in refs [21, 22, 36, 37]). Figure 3 summarizes the virological events that occur during the eclipse phase where the ‘window of opportunity’ is key for blocking acquisition. Passive immunization studies in NHPs

using neutralizing antibodies suggest that the window of opportunity is 24 hr at most.[38, 39] Transmission across the mucosal epithelium is thought to occur within hours of exposure and results in infectious virus reaching susceptible CD4+ target cells. Transmission selleck chemicals across the mucosal barrier can be passive through epithelial breaks but an active transport mechanism is also known.[40] The nature of the first infected type of CD4+ cell has been debated over the years but recent acute transmission studies strongly suggest that it is a CD4+ CCR5+ memory T cell.[41, 42] Strikingly, most HIV infections are due to a single founder virus,[41, 42] which is also true for model AIDS viruses in NHPs.[41] It takes approximately 24 hr for an infected CD4+ cell to produce infectious virus,[43]

so it is likely that the earliest time that HIV can start to spread to other CD4+ CCR5+ T cells is within the first 24–28 hr, a small number of local infected founder cells 2–3 days after exposure[44, 45] (Fig. 3). Local expansion of the infected founder cells occurs around days 4 to 5 post-exposure,[44, 45] likely aided by an innate response of the mucosal epithelium that attracts additional triclocarban target cells to the site (ref. [46] and discussed in ref. [36]). Virus or virus-infected cells from the local expansion spread via afferent lymphatics to the draining lymph node, which is rich in additional CD4+ CCR5+ target cells. From there, virus and infected cells spread systemically via the thoracic duct leading to distal and propagating infections in the gut and spleen by haematogenous flow and finally back to lymph nodes. Once the infection spreads from the local focus, it is very likely that the window of opportunity is closed because of the establishment of viral reservoirs and protective niches in distal tissues. The systemic spread of infection ultimately leads to plasma viral loads that cross the 100 copy limit of sensitivity (i.e.