Association between the cytokine storm, immune cell dynamics, and viral replicative capacity in hyperacute HIV infection.

Autor: Muema DM; Africa Health Research Institute, Durban, South Africa.; HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.; KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya., Akilimali NA; Africa Health Research Institute, Durban, South Africa., Ndumnego OC; Africa Health Research Institute, Durban, South Africa., Rasehlo SS; Africa Health Research Institute, Durban, South Africa., Durgiah R; Africa Health Research Institute, Durban, South Africa., Ojwach DBA; HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa., Ismail N; HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa., Dong M; HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa., Moodley A; HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa., Dong KL; HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.; Ragon Institute of MGH, MIT and Harvard University, Cambridge, MA, USA., Ndhlovu ZM; Africa Health Research Institute, Durban, South Africa.; HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.; Ragon Institute of MGH, MIT and Harvard University, Cambridge, MA, USA., Mabuka JM; Africa Health Research Institute, Durban, South Africa., Walker BD; HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.; Ragon Institute of MGH, MIT and Harvard University, Cambridge, MA, USA., Mann JK; HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa., Ndung'u T; Africa Health Research Institute, Durban, South Africa. thumbi.ndungu@ahri.org.; HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa. thumbi.ndungu@ahri.org.; Ragon Institute of MGH, MIT and Harvard University, Cambridge, MA, USA. thumbi.ndungu@ahri.org.; Max Planck Institute for Infection Biology, Berlin, Germany. thumbi.ndungu@ahri.org.; Division of Infection and Immunity, University College London, London, UK. thumbi.ndungu@ahri.org.
Jazyk: angličtina
Zdroj: BMC medicine [BMC Med] 2020 Mar 25; Vol. 18 (1), pp. 81. Date of Electronic Publication: 2020 Mar 25.
DOI: 10.1186/s12916-020-01529-6
Abstrakt: Introduction: Immunological damage in acute HIV infection (AHI) may predispose to detrimental clinical sequela. However, studies on the earliest HIV-induced immunological changes are limited, particularly in sub-Saharan Africa. We assessed the plasma cytokines kinetics, and their associations with virological and immunological parameters, in a well-characterized AHI cohort where participants were diagnosed before peak viremia.
Methods: Blood cytokine levels were measured using Luminex and ELISA assays pre-infection, during the hyperacute infection phase (before or at peak viremia, 1-11 days after the first detection of viremia), after peak viremia (24-32 days), and during the early chronic phase (77-263 days). Gag-protease-driven replicative capacities of the transmitted/founder viruses were determined using a green fluorescent reporter T cell assay. Complete blood counts were determined before and immediately following AHI detection before ART initiation.
Results: Untreated AHI was associated with a cytokine storm of 12 out of the 33 cytokines analyzed. Initiation of ART during Fiebig stages I-II abrogated the cytokine storm. In untreated AHI, virus replicative capacity correlated positively with IP-10 (rho = 0.84, P < 0.001) and IFN-alpha (rho = 0.59, P = 0.045) and inversely with nadir CD4 + T cell counts (rho = - 0.58, P = 0.048). Hyperacute HIV infection before the initiation of ART was associated with a transient increase in monocytes (P < 0.001), decreased lymphocytes (P = 0.011) and eosinophils (P = 0.003) at Fiebig stages I-II, and decreased eosinophils (P < 0.001) and basophils (P = 0.007) at Fiebig stages III-V. Levels of CXCL13 during the untreated hyperacute phase correlated inversely with blood eosinophils (rho = - 0.89, P < 0.001), basophils (rho = - 0.87, P = 0.001) and lymphocytes (rho = - 0.81, P = 0.005), suggesting their trafficking into tissues. In early treated individuals, time to viral load suppression correlated positively with plasma CXCL13 at the early chronic phase (rho = 0.83, P = 0.042).
Conclusion: While commencement of ART during Fiebig stages I-II of AHI abrogated the HIV-induced cytokine storm, significant depletions of eosinophils, basophils, and lymphocytes, as well as transient expansions of monocytes, were still observed in these individuals in the hyperacute phase before the initiation of ART, suggesting that even ART initiated during the onset of viremia does not abrogate all HIV-induced immune changes.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje