Dengue virus is an important human pathogen, infecting an estimated 400 million individuals per year and causing symptomatic disease in a subset of approximately 100 million. Much of the effort to date describing the host response to dengue has focused on the adaptive immune response, in part because of the well-established roles of antibodydependent enhancement and T cell original sin as drivers of severe dengue upon heterotypic secondary infection. However, the innate immune system is a crucial factor in the host response to dengue, as it both governs the fate and vigor of the adaptive immune response, and mediates the acute inflammatory response in tissues. In this review, we discuss the innate inflammatory response to dengue infection, focusing on the role of evolutionarily conserved innate immune cells, their effector functions, and clinical course.

Human immunodeficiency virus (HIV) is a retrovirus which became pandemic in the early 1980s. Since its initial characterization, advancements in diagnosis and management have transformed HIV infection from a terminal diagnosis to a chronic, manageable condition. Effective antiretroviral therapy, acting at multiple steps in the viral lifecycle, durably suppresses viral replication, preserves maternal health and prevents mother to child HIV transmission. Here, we review the salient clinical and ethical considerations of managing HIV infection during pregnancy and delivery.

SARS-CoV-2 represents an unprecedented public health challenge. While the majority of SARS-CoV-2-infected individuals with mild-to-moderate COVID-19 resolve their infection with few complications, some individuals experience prolonged symptoms lasting for weeks after initial diagnosis. Persistent viral infections are commonly accompanied by immunologic dysregulation, but it is unclear if persistent COVID-19 impacts the development of virus-specific cellular immunity. To this end, we analyzed SARS-CoV-2-specific cellular immunity in convalescent COVID-19 patients who experienced eight days or fewer of COVID-19 symptoms or symptoms persisting for 18 days or more. We observed that persistent COVID-19 symptoms were not associated with the development of an overtly dysregulated cellular immune response. Furthermore, we observed that reactivity against the N protein from SARS-CoV-2 correlates with the amount of reactivity against the seasonal human coronaviruses 229E and NL63. These results provide insight into the processes that regulate the development of cellular immunity against SARS-CoV-2 and related human coronaviruses.

Dengue virus (DENV) is a prevalent human pathogen, infecting approximately 400 million individuals per year and causing symptomatic disease in approximately 100 million. A distinct feature of dengue is the increased risk for severe disease in some individuals with preexisting DENV-specific immunity. One proposed mechanism for this phenomenon is antibody-dependent enhancement (ADE), in which poorly-neutralizing IgG antibodies from a prior infection opsonize DENV to increase infection of Fc gamma receptor-bearing cells. While IgM and IgG are the most commonly studied DENV-reactive antibody isotypes, our group and others have described the induction of DENV-specific serum IgA responses during dengue. We hypothesized that monomeric IgA would be able to neutralize DENV without the possibility of ADE. To test this, we synthesized IgG and IgA versions of two different DENV-reactive monoclonal antibodies. We demonstrate that isotype-switching does not affect the antigen binding and neutralization properties of the two mAbs. We show that DENV-reactive IgG, but not IgA, mediates ADE in Fc gamma receptor-positive K562 cells. Furthermore, we show that IgA potently antagonizes the ADE activity of IgG. These results suggest that levels of DENV-reactive IgA induced by DENV infection might regulate the overall IgG mediated ADE activity of DENV-immune plasma in vivo, and may serve as a predictor of disease risk.

Dengue virus (DENV) is endemic in over 100 countries, infecting an estimated 400 million individuals every year. Infection with DENV raises an antibody response primarily targeting viral structural proteins. However, DENV encodes several immunogenic non-structural (NS) proteins, one of which, NS1, is expressed on the membrane of DENV-infected cells. IgG and IgA isotype antibodies that bind NS1 are abundant in serum following DENV infection. Our study aims to determine if NS1-binding IgG and IgA isotype antibodies contribute to the clearance of DENV-infected cells by antibody-mediated cellular phagocytosis. We observed that both IgG and IgA isotype antibodies can facilitate monocytic uptake of DENV NS1 expressing cells in a FcγRI and FcαRI dependent fashion. Interestingly, this process was antagonized by the presence of soluble NS1, suggesting that the production of soluble NS1 by infected cells may serve as immunological chaff, antagonizing opsonization and clearance of DENV infected cells.