Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that induces in humans a disease characterized by fever, rash, and pain in muscles and joints. The recent emergence or reemergence of CHIKV in the Indian Ocean Islands and India has stressed the need to better understand the pathogenesis of this disease. Previous CHIKV disease models have used young or immunodeficient mice, but these do not recapitulate human disease patterns and are unsuitable for testing immune-based therapies. Herein, we describe what we believe to be a new model for CHIKV infection in adult, immunocompetent cynomolgus macaques. CHIKV infection in these animals recapitulated the viral, clinical, and pathological features observed in human disease. In the macaques, long-term CHIKV infection was observed in joints, muscles, lymphoid organs, and liver, which could explain the long-lasting CHIKV disease symptoms observed in humans. In addition, the study identified macrophages as the main cellular reservoirs during the late stages of CHIKV infection in vivo. This model of CHIKV physiopathology should allow the development of new therapeutic and/or prophylactic strategies.

Plasmacytoid dendritic cells (pDCs) are antigen-presenting cells that develop into type-I interferon (IFN-I IntroductionPlasmacytoid dendritic cells (pDCs) are major type I interferon (IFN-I) producing cells in response to viral infections 1 as a result of selective expression of Toll-like receptors 7 and 9 and constitutive expression of interferon response factor 7. They migrate to inflamed lymph nodes (LN) through high endothelium venules during viral and bacterial infections 2,3 and provide an important link between innate and adaptive immunity, enhancing natural killer (NK) cell activity and adaptive immune responses.Blood pDC counts and pDC-dependent IFN-I production levels in vitro decrease in patients infected with human immunodeficiency virus (HIV). [4][5][6][7][8] These decreases are generally correlated with a fall in CD4 ϩ T-cell counts, inversely correlated with plasma viral load, and are associated with opportunistic infections. 5,6,[9][10][11][12] The reduction in circulating pDC numbers during HIV infection may be related to their direct infection, 6,9,13 or to redistribution to lymphoid organs, as suggested in the chronic asymptomatic stage of HIV infection. 14 In nonhuman primate models of HIV infection, the IFN-I innate response is an early immunologic event. [15][16][17] Rhesus macaque (Macaca mulatta) pDCs are activated and produce IFN-I in vitro in response to pathogenic simian immunodeficiency virus (SIV) 18,19 like their human counterparts in response to HIV. 20,21 Strong depletion of pDCs from blood and lymphoid tissues are reported in the end stage of SIV infection 19,22 and attributed to infection and to higher levels of apoptosis.However, although the HIV/SIV interplay with the host immune response during primary infection is a key event, probably determining the later progression to disease, little is known about the role of pDCs in immune regulation at this early stage.We predicted that HIV/SIV infection may have an impact on the dynamics of circulating and LN dendritic cells (DCs) and on their functions in the first few days of infection 23,24 and that it may induce immune suppression through IFN-I production and indoleamine-2,3-dioxygenase (IDO) activity. IDO is the ratelimiting enzyme responsible for the extrahepatic catabolism of the essential amino acid tryptophan (Trp) and is triggered by type I and type II interferons. [25][26][27] Abnormal production/activation of IDO is associated with inefficient immunologic responses to infections, including HIV/SIV and cancer 26,[28][29][30] and is induced by HIV in human pDCs in vitro. 20,21 Growing evidence suggests that pDCs are involved in the induction of tolerance through IDO-dependent mechanisms. 31 This suggests that pDCs may target immune suppression during the acute phase of HIV/SIV infection.We focused on the dynamics of pDCs during primary infection by carrying out fine time-resolution sampling of blood, and a longitudinal analysis of peripheral lymph nodes, using absolute quantification, to investigate the possible homing of ...

The current pandemic of coronavirus disease (COVID) 2019 constitutes a global public health issue. Regarding the emerging importance of the gut-lung axis in viral respiratory infections, analysis of the gut microbiota's composition and functional activity during a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection might be instrumental in understanding and controling COVID 19. We used a nonhuman primate model (the macaque), that recapitulates mild COVID-19 symptoms, to analyze the effects of a SARS-CoV-2 infection on dynamic changes of the gut microbiota. 16S rRNA gene profiling and analysis of β diversity indicated significant changes in the composition of the gut microbiota with a peak at 10-13 days post-infection (dpi). Analysis of bacterial abundance correlation networks confirmed disruption of the bacterial community at 10-13 dpi. Some alterations in microbiota persisted after the resolution of the infection until day 26. Some changes in the relative bacterial taxon abundance associated with infectious parameters. Interestingly, the relative abundance of Acinetobacter (Proteobacteria) and some genera of the Ruminococcaceae family (Firmicutes) was positively correlated with the presence of SARS-CoV-2 in the upper respiratory tract. Targeted quantitative metabolomics indicated a drop in short-chain fatty acids (SCFAs) and changes in several bile acids and tryptophan metabolites in infected animals. The relative abundance of several taxa known to be SCFA producers (mostly from the Ruminococcaceae family) was negatively correlated with systemic inflammatory markers while the opposite correlation was seen with several members of the genus Streptococcus. Collectively, SARS-CoV-2 infection in a nonhuman primate is associated with changes in the gut microbiota's composition and functional activity.