title: Limited CD4+ T cell proliferation leads to preservation of CD4+ T cell counts in SIV-infected sooty mangabeys.
abstract: Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections result in chronic virus replication and progressive depletion of CD4+ T cells, leading to immunodeficiency and death. In contrast, 'natural hosts' of SIV experience persistent infection with high virus replication but no severe CD4+ T cell depletion, and remain AIDS-free. One important difference between pathogenic and non-pathogenic infections is the level of activation and proliferation of CD4+ T cells. We analysed the relationship between CD4+ T cell number and proliferation in HIV, pathogenic SIV in macaques, and non-pathogenic SIV in sooty mangabeys (SMs) and mandrills. We found that CD4+ T cell proliferation was negatively correlated with CD4+ T cell number, suggesting that animals respond to the loss of CD4+ T cells by increasing the proliferation of remaining cells. However, the level of proliferation seen in pathogenic infections (SIV in rhesus macaques and HIV) was much greater than in non-pathogenic infections (SMs and mandrills). We then used a modelling approach to understand how the host proliferative response to CD4+ T cell depletion may impact the outcome of infection. This modelling demonstrates that the rapid proliferation of CD4+ T cells in humans and macaques associated with low CD4+ T cell levels can act to 'fuel the fire' of infection by providing more proliferating cells for infection. Natural host species, on the other hand, have limited proliferation of CD4+ T cells at low CD4+ T cell levels, which allows them to restrict the number of proliferating cells susceptible to infection.
authors.affiliation: Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Kensington, NSW, Australia.
authors.forename: Ming Liang
authors.initials: ML
authors.lastname: Chan
authors.forename: Janka
authors.initials: J
authors.lastname: Petravic
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Ortiz
authors.forename: Jessica
authors.initials: J
authors.lastname: Engram
authors.forename: Mirko
authors.initials: M
authors.lastname: Paiardini
authors.forename: Deborah
authors.initials: D
authors.lastname: Cromer
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
authors.forename: Miles P
authors.initials: MP
authors.lastname: Davenport
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D049109:Cell Proliferation; D016665:Cercocebus atys / Q000276:immunology* / Q000821:virology; D005434:Flow Cytometry; D019394:Ki-67 Antigen / Q000097:blood; D018448:Models, Immunological; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D018709:Statistics, Nonparametric; D014779:Virus Replication / Q000276:immunology
chemical_list: D019394:Ki-67 Antigen