Intestinal Enteroids Support Human Adenovirus Replication
Human enteroids, a primary intestinal epithelial culture system, are being developed to cultivate enteric viruses and study host responses to viral infection. Holly and Smith (e00250-18) added human adenovirus to the repertoire of fastidious enteric viruses that replicate in human enteroids. Adenovirus replication is sensitive to interferon in these primary cells, and a respiratory serotype has a preference for goblet cells. This innovation demonstrates the power of enteroids in uncovering aspects of host-pathogen interactions previously unattainable with standard cell lines and suggests that enteroids may be a unified platform for culturing enteric viruses.
Respiratory human adenovirus (HAdV-5p) preferentially infects goblet cells (GC) in human enteroids.
Reversal of HIV-1 Latency by Maraviroc through NF-κB Activation
Maraviroc is a CCR5 antagonist used in the treatment of HIV-1 infection. Madrid-Elena et al. (e01931-17) discovered that maraviroc reactivates latent HIV-1 in a clinical trial of maraviroc intensification in antiretroviral therapy (ART)-suppressed HIV-1-infected patients. Maraviroc increases activation of NF-κB and HIV-1 transcription in resting CD4+ T cells, as determined by detection of HIV-1 unspliced RNA. The direct binding of maraviroc to CCR5 acts as a partial agonist. These findings support the use of maraviroc as a latency-reversing agent to eliminate viral reservoirs in resting CD4+ T cells in HIV-1-infected patients.
Maraviroc promotes HIV-1 latency reversal in resting CD4+ T cells.
Protein Evolution in Poliovirus Capsid Domains
Numerous antigenic poliovirus variants emerged during a Nigerian outbreak. However, overall antigenic evolution was limited, despite a high evolution rate. Shaw et al. (e01949-17) analyzed amino acid replacements in five capsid functional domains during a large circulating type 2 vaccine-derived outbreak. Poliovirus capsid evolution at the amino acid level is constrained. Sites mapping to the variable VP1 amino terminus region retain a predicted amphipathic helix. Residues binding the poliovirus receptor and residues mapping to the structural core region were strongly conserved. These findings provide insights into structure-function relationships in capsid protein evolution.
Heat map illustrating the frequency of neutralizing antigenic (NAg) amino acid replacements mapped to the X-ray crystallographic structure of the poliovirus type 2 capsid pentamer.
Human Cytomegalovirus UL8 Protein Acts as a Cytokine Suppressor
A large proportion of the human cytomegalovirus (HCMV) genome encodes products that counteract host immune surveillance and responses at all stages of replication. Pérez-Carmona et al. (e02229-17) characterized UL8, a heavily glycosylated, cell surface HCMV protein. The immunoglobulin-like domain of UL8 restricts the production of many proinflammatory factors in myeloid cells late in infection. These findings suggest that UL8 subverts host immune control and contributes to HCMV persistence.
Kinetics of IL-8 secretion in THP-1 cells infected with an HCMV mutant lacking the UL8 gene.