The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome’s low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153, OPG204, and OPG208, could be affected in a manner consistent with the established “genomic accordion” evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability.

In developing countries, Epstein-Barr virus (EBV) infection is mostly asymptomatic in early childhood. EBV persistence may lead to different malignancies, such as B cell derived lymphomas. In Argentina, most children are seropositive at three years and an increased association between EBV and lymphoma was proved in children under 10 years old by our group. Our aim was to characterize EBV infection at the site of entry and reactivation of viral infection -the tonsils- in order to better understand the mechanism of viral persistence in pediatric patients. A cohort of 54 patients was described. We assessed specific antibodies profiles in sera; viral proteins presence by IHC on FFPE samples and EBV type from fresh tissue. EBV type 1 was prevalent, mostly in the youngest patients. Asymptomatic primary infected patients presented higher viral loads and Latency 0/I or II patterns, whereas the Latency III pattern was observed mostly in healthy carriers. There were no differences between groups in the expression of viral lytic antigens. This study discloses new features in patients undergoing primary infection from a developing population. Low viral inoculum and restricted viral antigen expression may be responsible for the lack of symptoms in children from our country.

Most studies on Epstein Barr virus (EBV) primary infection have been performed in adolescents and young adult populations with Infectious Mononucleosis (IM) in developed countries. Furthermore, studies related to macrophage polarization were assessed in EBV-associated lymphomas, but little is known about macrophage polarization in the context of primary infection at the site of viral entry and replication, the tonsils.

Macrophages are exceptionally flexible cells. The presence of inflammatory cytokines such as IFN-γ and TNF-α results in an M1 (CD68) activation, while cytokines such as IL-10 or TGF-β induce the M2 (CD163) activation. Our aim was to study the behavior of peripheral cytokines involved in macrophage polarization and relate them with tissue findings to further comprehend the role of macrophages in EBV pediatric infection. We studied cytokine expression in tonsils and peripheral blood samples of children in different stages of infection. Peripheral cytokines were compared with macrophage polarization markers and viral protein expression in tonsils. Only IL-10 showed a negative correlation between compartments, exclusively in patients undergoing viral reactivation (R). Higher expressions of peripheral IL-1β, IL-23, and IL-12p40 in R children were observed. Lower expressions of local and peripheral TNF-α in patients with broader expressions of latent and lytic viral proteins were demonstrated. In healthy carrier (HC) patients, IL-23 positively correlated with CD163, and IP-10 positively correlated with CD68. Our results indicated that EBV might modulate antigen expression in the presence of TNF-α and influence peripheral cytokine expression differently in each stage of infection. Moreover, peripheral cytokines might have a particular role in macrophage polarization in HC.

In Argentina, a high incidence of EBV-associated lymphomas was demonstrated in young children. Natural killer (NK) cells, particularly, IFN-γ-producing CD56bright NK cells, have been reported to play a key role in asymptomatic EBV infection in children, restricting viral-mediated transformation. In order to analyze NK cell characteristics in children with primary and persistent EBV infection, along with EBV+ Hodgkin lymphoma (HL) from Argentina, a cohort of EBV-infected pediatric patients was analyzed. A scarcity of CD56+ cells, as an indirect marker of NK cells, across all tonsillar samples and pediatric classical Hodgkin lymphoma cases was observed, with no significant differences according to EBV status. In primary infection, CD56+ cells showed a positive correlation with IFNγ+ cells, suggesting a role in early antiviral responses. Flow cytometry revealed an increased proportion of CD56bright NK cells in EBV-infected children, particularly in cases expressing latency II/III antigens. A significantly higher IFN-γ production was observed in CD56bright cells in children with primary infection compared with healthy carriers, along with an inverse correlation between IFN-γ production and CD56bright cells in healthy carriers. These findings suggest that NK cells may contribute to immune control predominantly during primary infection, whereas their role appears limited in healthy carriers and in EBV-associated Hodgkin lymphoma.