Widespread, human-associated redondoviruses infect the commensal protozoan Entamoeba gingivalis.

Redondoviruses are circular Rep-encoding single-stranded DNA (CRESS) viruses of high prevalence in healthy humans. Redondovirus abundance is increased in oro-respiratory samples from individuals with periodontitis, acute illness, and severe COVID-19. We investigated potential host cells supporting redondovirus replication in oro-respiratory samples and uncovered the oral amoeba Entamoeba gingivalis as a likely host. Redondoviruses are closely related to viruses of Entamoeba and contain reduced GC nucleotide content, consistent with Entamoeba hosts. Redondovirus and E. gingivalis co-occur in metagenomic data from oral disease and healthy human cohorts. When grown in xenic cultures with feeder bacteria, E. gingivalis was robustly positive for redondovirus RNA and DNA. A DNA proximity-ligation assay (Hi-C) on xenic culture cells showed enriched cross-linking of redondovirus and Entamoeba DNA, supporting E. gingivalis as the redondovirus host. While bacteria are established hosts for bacteriophages within the human virome, this work shows that eukaryotic commensals also contribute an abundant human-associated virus.

Highly restricted SARS-CoV-2 receptor expression and resistance to infection by primary human monocytes and monocyte-derived macrophages.

Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV2), which causes the disease COVID-19, has caused an unprecedented global pandemic. Angiotensin-converting enzyme 2 (ACE2) is the major cellular receptor for SARS-CoV2 entry, which is facilitated by viral Spike priming by cellular TMPRSS2. Macrophages play an important role in innate viral defense and are also involved in aberrant immune activation that occurs in COVID-19, and thus direct macrophage infection might contribute to severity of SARS-CoV2 infection. Here, we demonstrate that monocytes and monocyte-derived macrophages (MDM) under in vitro conditions express low-to-undetectable levels of ACE2 and TMPRSS2 and minimal coexpression. Expression of these receptors remained low in MDM induced to different subtypes such as unpolarized, M1 and M2 polarized. Untreated, unpolarized, M1 polarized, and M2 polarized MDM were all resistant to infection with SARS-CoV2 pseudotyped virions. These findings suggest that direct infection of myeloid cells is unlikely to be a major mechanism of SARS-CoV2 pathogenesis. Summary sentence: Monocytes and macrophages express minimal ACE2 and TMPRSS2 and resist SARS-CoV-2 Spike-mediated infection, suggesting direct myeloid cell infection is unlikely a major contributor to pathogenesis.