Mem Inst Oswaldo Cruz, Rio de Janeiro, VOLUME 119 | 2024
Research Articles
HSV1-induced enhancement of productive HIV-1 replication is associated with interferon pathway downregulation in human macrophages
1Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Imunofarmacologia, Rio de Janeiro, RJ, Brasil
2Fundação Oswaldo Cruz-Fiocruz, Instituto Nacional de Ciência e Tecnologia de Inovação em Doenças de Populações Negligenciadas, Centro de Desenvolvimento Tecnológico em Saúde, Rio de Janeiro, RJ, Brasil
3Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Rio de Janeiro, RJ, Brasil
4Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Morfologia e Morfogênese Viral, Rio de Janeiro, RJ, Brasil
DOI: 10.1590/0074-02760240102
ABSTRACT
BACKGROUND Herpesviruses are common co-pathogens in individuals infected with human immunodeficiency virus (HIV). Herpes simplex virus type 1 (HSV1) enhances HIV-1 replication and has evolved mechanisms to evade or disrupt host innate immune responses, including interference with interferon (IFN) signalling pathways.
OBJECTIVES The aimed of this work was evaluated whether it HSV1 affects HIV-1 replication through the modulation of the IFN pathway in human macrophages.
METHODS Co-infections with HSV1 and HIV-1 were performed in monocyte-derived human macrophages (hMDMs). The production of infectious HIV-1 and HSV-1 was monitored 48 h post-coinfection. Additionally, mRNA and protein expression levels of interferon-stimulated genes (ISGs) were evaluated in both HIV-1-HSV1 coinfections and HSV1 mono-infections.
FINDINGS The HSV1 coinfection increasing the HIV-1 productive replication, following of downregulation of interferon-alpha (IFN-α) and interferon-induced transmembrane protein 3 (IFITM3) expression in hMDMs. Acyclovir treatment, in a dose-dependent manner, mitigated HSV1’s ability to decrease IFITM3 levels. Knockdown of HSV1 Us11 and virion host shutoff (VHS) genes reactivated the IFN pathway, evidenced by restored IFITM3 expression and activation of eIF2-α and PKR. This knockdown also returned HIV-1 replication to baseline levels.
MAIN CONCLUSIONS Our data suggested that HSV1 increases HIV-1 replication in human macrophages is associated with the downregulating interferon pathways and ISGs expression.
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Financial support: CNPq, CAPES, FAPERJ.
VMA and FP-D contributed equally to this work.
+ Corresponding author: thiago.moreno@fiocruz.br 
https://orcid.org/0000-0003-2212-3899
Received 02 May 2024
Accepted 05 September 2024
HOW TO CITE
Andrade VM, Pereira-Dutra F, Abrantes JL, Miranda MD, Souza TML. HSV1-induced enhancement of productive HIV-1 replication is associated with interferon pathway downregulation in human macrophages. Mem Inst Oswaldo Cruz. 2024; 119: e240102.
