Mechanisms of reactivation of latent tuberculosis infection due to SIV coinfection

HIV is a major driver of tuberculosis (TB) reactivation. Depletion of CD4+ T cells is assumed to be the basis behind TB reactivation in individuals with latent tuberculosis infection (LTBI) coinfected with HIV. Nonhuman primates (NHPs) coinfected with a mutant simian immunodeficiency virus (SIVΔGY) that does not cause depletion of tissue CD4+ T cells during infection failed to reactivate TB. To investigate the contribution of CD4+ T cell depletion relative to other mechanisms of SIV-induced reactivation of LTBI, we used CD4R1 antibody to deplete CD4+ T cells in animals with LTBI without lentiviral infection. The mere depletion of CD4+ T cells during LTBI was insufficient in generating reactivation of LTBI. Instead, direct cytopathic effects of SIV resulting in chronic immune activation, along with the altered effector T cell phenotypes and dysregulated T cell homeostasis, were likely mediators of reactivation of LTBI. These results revealed important implications for TB control in HIV-coinfected individuals

Amplification dynamics of platy-1 retrotransposons in the cebidae platyrrhine lineage

© 2019 The Author(s). Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. Platy-1 elements are Platyrrhine-specific, short interspersed elements originally discovered in the Callithrix jacchus (common marmoset) genome. To date,only themarmoset genomehas been analyzed for Platy-1 repeat content.Here,we report full-length Platy-1 insertions in other NewWorld monkey (NWM) genomes (Saimiri boliviensis, squirrel monkey; Cebus imitator, capuchin monkey; and Aotus nancymaae, owl monkey) and analyze the amplification dynamics of lineage-specific Platy-1 insertions. A relatively small number of full-length and lineage-specific Platy-1 elements were found in the squirrel, capuchin, and owl monkey genomes compared with the marmoset genome. In addition, only a few older Platy-1 subfamilies were recovered in this study, with no Platy-1 subfamilies younger than Platy-1-6. By contrast, 62 Platy-1 subfamilieswere discovered in themarmoset genome.All of the lineagespecific insertions found in the squirrel and capuchin monkeys were fixed present. However, 15%of the lineage-specific Platy-1 loci in Aotus were polymorphic for insertion presence/absence. In addition, two new Platy-1 subfamilies were identified in the owl monkey genome with low nucleotide divergences compared with their respective consensus sequences, suggesting minimal ongoing retrotransposition in the Aotus genus and no current activity in the Saimiri, Cebus, and Sapajus genera. These comparative analyses highlight the finding that the high number of Platy-1 elements discovered in themarmoset genome is an exception among NWManalyzed thus far, rather than the rule. Future studies are needed to expand upon our knowledge of Platy-1 amplification in other NWM genomes