Chikungunya virus (CHIKV) is an arthropod-borne virus (arbovirus) of epidemic concern, transmitted by Aedes ssp. mosquitoes, and is the etiologic agent of a febrile and incapacitating arthritogenic illness responsible for millions of human cases worldwide. After major outbreaks starting in 2004, CHIKV spread to subtropical areas and western hemisphere coming from sub-Saharan Africa, South East Asia, and the Indian subcontinent. Even though CHIKV disease is self-limiting and non-lethal, more than 30% of the infected individuals will develop chronic disease with persistent severe joint pain, tenosynovitis, and incapacitating polyarthralgia that can last for months to years, negatively impacting an individual’s quality of life and socioeconomic productivity. The lack of specific drugs or licensed vaccines to treat or prevent CHIKV disease associated with the global presence of the mosquito vector in tropical and temperate areas, representing a possibility for CHIKV to continually spread to different territories, make this virus an agent of public health burden. In South America, where Dengue virus is endemic and Zika virus was recently introduced, the impact of the expansion of CHIKV infections, and co-infection with other arboviruses, still needs to be estimated. In Brazil, the recent spread of the East/Central/South Africa (ECSA) and Asian genotypes of CHIKV was accompanied by a high morbidity rate and acute cases of abnormal disease presentation and severe neuropathies, which is an atypical outcome for this infection. In this review, we will discuss what is currently known about CHIKV epidemics, clinical manifestations of the human disease, the basic concepts and recent findings in the mechanisms underlying virus-host interaction, and CHIKV-induced chronic disease for both in vitro and in vivo models of infection. We aim to stimulate scientific debate on how the characterization of replication, host-cell interactions, and the pathogenic potential of the new epidemic viral strains can contribute as potential developments in the virology field and shed light on strategies for disease control.

The development of persistent cellular reservoirs of latent human immunodeficiency virus (HIV) is a critical obstacle to viral eradication since viral rebound takes place once anti-retroviral therapy (ART) is interrupted. Previous studies show that HIV persists in myeloid cells (monocytes and macrophages) in blood and tissues in virologically suppressed people with HIV (vsPWH). However, how myeloid cells contribute to the size of the HIV reservoir and what impact they have on rebound after treatment interruption remain unclear. Here we report the development of a human monocyte-derived macrophage quantitative viral outgrowth assay (MDM-QVOA) and highly sensitive T cell detection assays to confirm purity. We assess the frequency of latent HIV in monocytes using this assay in a longitudinal cohort of vsPWH (n = 10, 100% male, ART duration 5–14 yr) and find half of the participants showed latent HIV in monocytes. In some participants, these reservoirs could be detected over several years. Additionally, we assessed HIV genomes in monocytes from 30 vsPWH (27% male, ART duration 5–22 yr) utilizing a myeloid-adapted intact proviral DNA assay (IPDA) and demonstrate that intact genomes were present in 40% of the participants and higher total HIV DNA correlated with reactivatable latent reservoirs. The virus produced in the MDM-QVOA was capable of infecting bystander cells resulting in viral spread. These findings provide further evidence that myeloid cells meet the definition of a clinically relevant HIV reservoir and emphasize that myeloid reservoirs should be included in efforts towards an HIV cure.