Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Neutralizing Abs target the receptor binding domain of the spike (S) protein, a focus of successful vaccine efforts. Concerns have arisen that S-specific vaccine immunity may fail to neutralize emerging variants. We show that vaccination with a human adenovirus type 5 vector expressing the SARS-CoV-2 nucleocapsid (N) protein can establish protective immunity, defined by reduced weight loss and viral load, in both Syrian hamsters and K18-hACE2 mice. Challenge of vaccinated mice was associated with rapid N-specific T cell recall responses in the respiratory mucosa. This study supports the rationale for including additional viral Ags in SARS-CoV-2 vaccines, even if they are not a target of neutralizing Abs, to broaden epitope coverage and immune effector mechanisms.

Ancestry shapes genetic immune responses: Selection for genes affecting the immune system can vary among populations because of selection for local environments. In humans, ancestry has been associated with different responses to infection. Randolph et al . examined the molecular determinants of these observations using single-cell RNA sequencing of immune cells from individuals of European and African descent who were infected with influenza in vitro. The experiments showed that infection-induced gene signatures diverged in a cell-type-specific manner that was correlated with ancestry, and that these observed ancestry-related differences were caused by changes in gene regulation and processes involved in transcription and translation. —LMZ

Numerous observations indicate that resident memory T cells (T_RM) undergo unusually rapid attrition within the lung. Here we demonstrate that contraction of lung CD8⁺ T cell responses after influenza infection is contemporized with egress of CD69⁺/CD103⁺ CD8⁺ T cells to the draining mediastinal LN via the lymphatic vessels, which we term retrograde migration. Cells within the draining LN retained canonical markers of lung T_RM, including CD103 and CD69, lacked Ly6C expression (also a feature of lung T_RM), maintained granzyme B expression, and did not equilibrate among immunized parabiotic mice. Investigations of bystander infection or removal of the TCR from established memory cells revealed that the induction of the T_RM phenotype was dependent on antigen recognition; however, maintenance was independent. Thus, local lung infection induces CD8⁺ T cells with a T_RM phenotype that nevertheless undergo retrograde migration, yet remain durably committed to the residency program within the draining LN, where they provide longer-lived regional memory while chronicling previous upstream antigen experiences.

The human airway epithelium is the initial site of SARS-CoV-2 infection. We used flow cytometry and single cell RNA-sequencing to understand how the heterogeneity of this diverse cell population contributes to elements of viral tropism and pathogenesis, antiviral immunity, and treatment response to remdesivir. We found that, while a variety of epithelial cell types are susceptible to infection, ciliated cells are the predominant cell target of SARS-CoV-2. The host protease TMPRSS2 was required for infection of these cells. Importantly, remdesivir treatment effectively inhibited viral replication across cell types, and blunted hyperinflammatory responses. Induction of interferon responses within infected cells was rare and there was significant heterogeneity in the antiviral gene signatures, varying with the burden of infection in each cell. We also found that heavily infected secretory cells expressed abundant IL-6, a potential mediator of COVID-19 pathogenesis.

Astroviruses are non-enveloped, single-stranded RNA viruses that infect mammalian and avian species. In humans, astrovirus infections are one of the most common causes of gastroenteritis in children. Infection has also been linked to serious neurological complications, especially in immunocompromised individuals. More extensive disease has also been characterized in non-human mammalian and avian species. To date, astroviruses have been detected in over 80 different avian and mammalian hosts. As the number of hosts continues to rise, the need to understand how astroviruses transmit within a given species as well as to new host species becomes increasingly important. Here, we review the current understanding of astrovirus transmission, the factors that influence viral spread, and the potential for cross-species transmission. Additionally, we highlight the current gaps in knowledge and areas of future research that will be key to understanding astrovirus transmission and zoonotic potential.