Abstract
The elderly population infected with HIV-1 is often characterized by the rapid AIDS progression and poor treatment outcome, possibly because of immunosenescence resulting from both HIV infection and aging. However, this hypothesis remains to be fully tested. Here, we studied 6 young and 12 old Chinese rhesus macaques (ChRM) over the course of three months after simian immunodeficiency virus (SIV) SIVmac239 infection. Old ChRM showed a higher risk of accelerated AIDS development than did young macaques, owing to rapidly elevated plasma viral loads and decreased levels of CD4+ T cells. The low frequency of naïve CD4+ T cells before infection was strongly predictive of an increased disease progression, whereas the severe depletion of CD4+ T cells and the rapid proliferation of naïve lymphocytes accelerated the exhaustion of naïve lymphocytes in old ChRM. Moreover, in old ChRM, a robust innate host response with defective regulation was associated with a compensation for naïve T cell depletion and a high level of immune activation. Therefore, we suggest that immunosenescence plays an important role in the accelerated AIDS progression in elderly individuals and that SIV-infected old ChRM may be a favorable model for studying AIDS pathogenesis and researching therapies for elderly AIDS patients.
Highlights
HIV is increasingly and extensively spreading among older individuals
To the 9.63 × copies/ml plasma in the young animals, a mean peak viral load of 1.58 × copies/ml plasma was found in the acute phase in the old Chinese rhesus macaques (ChRM) (P = 0.6468)
Because chronic diarrhea induced by increased intestinal permeability occurred during the progression of simian immunodeficiency virus (SIV) infection[24], it is conceivable that old ChRM may have a higher risk of rapid progression of AIDS
Summary
HIV is increasingly and extensively spreading among older individuals. Because an increased risk of HIV infection has been found in the elderly population, HIV-1-infected elderly patients have drawn great attention recently[1]. Increasing evidence suggests that a variety of HIV infection-induced immunologic alterations are similar to those seen in uninfected elderly people Most of these alterations often exhibit age-related abnormalities in adaptive immunity, including an accelerated decrease in T-cell renewal and an increase in B-cell exhaustion, an accumulation of terminally differentiated memory cells with poor proliferative responses, a shortened replication history, constricted diversity within the T-cell receptor (TCR) and B-cell receptor (BCR) repertoire and decreased responsiveness to vaccines. These outcomes result in a general decline in immunity, gradually giving rise to immunosenescence[4,5,6]. We compared the immunological, virological and gene-expression dynamics between young and old ChRM during early SIVmac[239] infection to identify the characteristics of elderly AIDS patients and to explore the interactions between immunosenescence and HIV/SIV infection
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 call
