The equivalence, however, of IgG levels in naive and latently infected TG suggests that CD4+ T cells were not absolutely required for this IgG entry. loaded with 50?ng of mock-infected Vero cell lysate, HSV-1 stock lysate, and purified gH/L, gB, gC, and gD. These blots were probed with TG homogenates made from (A) mouse HILDA samples and (B) human samples (ID no. 1A and 2A as referenced in Table?S1). (C) Western blot loaded with 50?ng of purified ICP4, ICP8, ICP27, UL30, UL42, and lysates from uninfected Dick-1 cells, Dick-1 cells infected with HSV-1 for 6?h, uninfected Vero cells, and Vero cells infected with HSV-1. The blot was probed with TG homogenate made from human samples. Download FIG?S2, TIF file, 1.3 MB. Copyright ? 2017 Jiang et al. This content is distributed under the terms of the Creative Commons Attribution 4.0 International license. TABLE?S1? Summary of adult human TG-IgG binding profiles. Human TG samples were obtained from autopsies. Each patient is denoted by a number, and individual TG in the pair are denoted by A and B. TG from the same individual (i.e., 2A and 2B) were processed and tested separately. The HSV-1 genome was assayed by PCR for HSV-1 gD. Modified Western blotting was performed on human samples as shown in Fig.?2D, and the IgG binding pattern to HSV antigens is summarized. Download TABLE?S1, TIF file, 0.2 MB. Copyright ? 2017 Jiang et al. This content is distributed under the terms of the Creative Commons Attribution 4.0 International license. FIG?S3? Passively administered IgG BRD-6929 accesses extravascular TG tissue. Immune sera were injected into naive or latently infected muMT mice, and perfused TG were BRD-6929 harvested at 18?h as in Fig.?3. (A to C) Representative IF images of TG from (A) uninjected naive muMT (negative control), (B) injected naive muMT, and (C) injected latently infected muMT mice that were stained for IgG (green), CD31/PECAM-1 (red), and DAPI (blue). Scale bars represent 100?m. Download FIG?S3, TIF file, 2.2 MB. Copyright ? 2017 Jiang et al. This content is distributed under the terms of the Creative Commons Attribution 4.0 International license. FIG?S4? PCR for HSV-1 genome in human fetal TG. DNA was extracted from human fetal TG, and PCR was BRD-6929 performed. (A) PCR for glycoprotein D with the expected band of 220?bp. (B) PCR for RNase P with the expected band of 80?bp. Controls: +, HSV genomes mixed with HEK293T DNA; ?, HEK293T DNA only; =, H2O control. Download FIG?S4, TIF file, 0.4 MB. Copyright ? 2017 Jiang et al. This content is distributed under the terms of the Creative Commons Attribution 4.0 International license. TEXT?S1? Supplemental methods. Download TEXT?S1, DOCX file, 0.01 MB. Copyright ? 2017 Jiang et al. This content is distributed under the terms of the Creative Commons Attribution 4.0 International license. ABSTRACT While antibody responses to neurovirulent pathogens are critical for clearance, the extent to which antibodies access the nervous system to ameliorate infection is poorly understood. In this study on herpes simplex virus 1 (HSV-1), we demonstrate that HSV-specific antibodies are present during HSV-1 latency in the nervous systems of both mice and humans. We show that antibody-secreting cells entered the trigeminal ganglion (TG), a key site of HSV infection, and persisted long after the establishment of latent infection. We also demonstrate the ability of passively administered IgG to enter the TG independently of infection, showing that the naive TG is accessible to antibodies. The translational implication of this finding is that human fetal neural tissue could contain HSV-specific maternally derived antibodies. Exploring this possibility, we observed HSV-specific IgG in HSV DNA-negative human fetal TG, suggesting passive transfer of maternal immunity into the prenatal nervous system. To further investigate the role of maternal antibodies in the neonatal nervous system, we established a murine model to demonstrate that maternal IgG can access and persist.