Abstract
Human immunodeficiency virus (HIV) infection is characterized by a dynamic process and highly variable progression. Although extensive comparisons have been reported between the minority of non-progressors (NPGs) and the majority of progressors (PGs), the underlying mechanism is still unclear. One reason for this is that the initial onset of infection is very difficult to track, particularly when men who have sex with men (MSM) are predominantly responsible for the transmission of human HIV. To find potential early protection strategies against later progression during chronic mucosal exposure, 10 Chinese-origin rhesus macaques (ChRhs) that underwent repetitive simian immunodeficiency virus (SIV) intrarectal exposure were longitudinally tracked. The results of the periodic detection of peripheral blood mononuclear cells (PBMCs) and colorectal mucosal lamina propria mononuclear cells (LPMCs) with immunoglobulins in rectal fluid were compared between non-progressive and progressive subgroups, which were classified based on their circulating viral loads. As a result, four NPGs and six PGs were observed after disease onset for 2 months. Upon comparing the mucosal and systemic immune responses, the PBMC response did not differ between the two subgroups. Regarding LPMCs, the increased activation of B1a/B1 cells among B cells and a peak in IgM in rectal fluid was observed approximately 10 days after the first exposure, followed by consistently low viremia in the four non-progressive ChRhs. In the six progressive ChRhs, neither B cell activation nor a peak in IgM was observed, while a robust elevation in IgG was observed, followed by consistently high viremia post exposure. Based on the PBMC-LPMC disparity between the subgroups of monkeys, we hypothesize that early B1 activation in LPMCs that result in an IgM peak might attenuate the entry and acquisition of SIV in the mucosa, resulting in very low dissemination into blood. Our models have suggested that the use of early surveillance both systemically and in the mucosa to comprehensively determine virus–host interactions would be informative for mucosal vaccine development.
Highlights
A tiny proportion of humans exposed to human immunodeficiency virus (HIV) retain a long-term non-progressive status and are known as “long-term non-progressors” (LTNPs) or “elite controllers” (ECs)
It has been documented that Chinese-origin rhesus macaques (ChRhs) are relatively resistant to simian immunodeficiency virus (SIV)-related progression, with approximately 30% of infected monkeys maintaining very low viral loads for several years (Ling et al, 2002)
As no well-acknowledged criteria for the viral load defining ECs/LTNPs/PGs status have been established in the ChRh model, as they have in HIV-infected humans, we classified the monkeys as either NPGs or PGs in the ChRh model
Summary
A tiny proportion of humans exposed to human immunodeficiency virus (HIV) retain a long-term non-progressive status and are known as “long-term non-progressors” (LTNPs) or “elite controllers” (ECs). Compared to the majority of those infected with HIV, who produce a strong virus-specific immune response and show obvious disease characteristics, LTNPs demonstrate extraordinarily low viral loads and do not progress to illness despite a lack of antiretroviral treatment (Sahu et al, 2001, 2005). Early mucosal immunity, which could potentially confer some protection to non-progressed MSM infectors, has not been revealed because it is extremely difficult to detect the primary response to mucosal exposure during HIV transmission. We employed Chinese-origin rhesus macaques (ChRhs) to generate spontaneous viral controllers with repeated low-dose simian immunodeficiency virus (SIV) exposure by the mucosal route. By tracking primary mucosal immunity, immune responses occurring from the entry point in the rectal mucosa to the peripheral blood were compared in parallel to find some informative clues about how the first barrier of mucosal immunity performs in future non-progressive controllers
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
