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Dhamapurkar, V.

Publications and source records attributed to Dhamapurkar, V..

2 recordsLinked to original sources
bioRxiv2026

Contemporary Victoria and Yamagata Influenza B Viruses Elicit Lineage-Specific Differences in Innate Immunity

The two influenza B virus (FLUBV) lineages, Victoria and Yamagata, have continued to diverge since their separation in the 1970s, resulting in distinct antigenic characteristics and differences in immunity and cross-protection. Human epidemiological observations and experimental studies have identified lineage-specific differences in adaptive immune responses elicited by contemporary viruses, suggesting that innate immune signaling may contribute to these divergent outcomes. To understand in-depth immunity to contemporary influenza B viruses, we compared viral replication, cytokine production, gene expression, and cellular tropism following infection with representative Victoria- and Yamagata-lineage viruses. We found that, despite broadly similar cytokine profiles in the ferret upper respiratory tract, the two lineages exhibited distinct innate immune kinetics. Yamagata viruses induced rapid early expression of antiviral and inflammatory genes, including SOCS1 and multiple interferon-stimulated genes, whereas Victoria viruses displayed delayed innate immune activation accompanied by greater viral replication. Consistent with the ferret data, Yamagata viruses also induced elevated SOCS1 expression in human PBMCs early after infection. In addition, Yamagata viruses exhibited broader cellular tropism, infecting a wider range of immune cell populations than Victoria viruses. Together, these findings demonstrate that contemporary influenza B virus lineages distinctly engage the host immune system and provide new insight into how lineage-specific innate immune responses may contribute to differences in immunity, cross-protection, and the divergent evolutionary trajectories of Victoria and Yamagata viruses

microbiology↗
bioRxiv2026

GM-CSF and M-CSF Driven Differentiation Differentially Regulates Chikungunya Virus Infection and Antiviral Responses in Human Monocyte-Derived Macrophages

Chikungunya virus is an arthritogenic alphavirus causing debilitating joint pain in infected individuals. The mechanisms driving CHIKV-associated arthralgia is poorly understood, however, macrophages have been implicated as potential reservoirs of persistent viral material and mediators of immunopathology. Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) and Macrophage-Colony Stimulating Factor (M-CSF) are cytokines that serve as myeloid growth factors that bias macrophages toward pro-inflammatory and anti-inflammatory phenotypes, respectively. In this study, we examined how cytokine-driven macrophage differentiation via GM-CSF and M-CSF influences susceptibility to and responses against CHIKV infection in vitro. Using parallel donor-matched cultures of primary macrophages, we show that GM-CSF-differentiated macrophages are highly permissive to CHIKV and Mayaro virus (MAYV) infection and support robust viral replication, whereas M-CSF-differentiated macrophages are resistant to CHIKV replication and lack detectable levels of viral protein expression. Despite these differences, we observed pro-inflammatory, M1-skewing of CHIKV-infected macrophages, regardless of differentiation state. Interestingly, we observe higher production of IFN and IP10/CXCL10 in M-CSF differentiated macrophages, suggesting that M-CSF promotes an antiviral state that restricts CHIKV infection. Stimulation of macrophages with double-stranded RNA (polyinosinic:polycytidylic acid; poly(I:C)), but not with single-stranded RNA (resiquimod, R848), recapitulated the antiviral cytokine and chemokine response induced by CHIKV infection. These findings suggest that dsRNA sensing plays a more prominent role than ssRNA sensing in driving the macrophage antiviral response to CHIKV. Together, these findings highlight macrophage differentiation as a critical determinant of CHIKV susceptibility and antiviral immunity in humans, with implications for understanding inflammatory pathogenesis during infection.

microbiology↗