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Resolving the role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in households with members from different generations is crucial for containing the current pandemic. We conducted a large-scale, multicenter, cross-sectional seroepidemiologic household transmission study in southwest Germany during May 11–August 1, 2020. We included 1,625 study participants from 405 households that each had ≥1 child and 1 reverse transcription PCR–confirmed SARS-CoV-2–infected index case-patient. The overall secondary attack rate was 31.6% and was significantly higher in exposed adults (37.5%) than in children (24.6%–29.2%; p = 60 years of age (72.9%; p = 0.039). Other risk factors for infectiousness of the index case-patient were SARS-CoV-2–seropositivity (odds ratio [OR] 27.8, 95% CI 8.26–93.5), fever (OR 1.93, 95% CI 1.14–3.31), and cough (OR 2.07, 95% CI 1.21–3.53). Secondary infections in household contacts generate a substantial disease burden.

BackgroundLong-term persistence of antibodies against SARS-CoV-2, particularly the SARS-CoV-2 Spike Trimer, determines individual protection against infection and potentially viral spread. The quality of children’s natural humoral immune response following SARS-CoV-2 infection is yet incompletely understood but crucial to guide pediatric SARS-CoV-2 vaccination programs.MethodsIn this prospective observational multi-center cohort study, we followed 328 households, consisting of 548 children and 717 adults, with at least one member with a previous laboratory-confirmed SARS-CoV-2 infection. The serological response was assessed at 3-4 months and 11-12 months after infection using a bead-based multiplex immunoassay for 23 human coronavirus antigens including SARS-CoV-2 and its Variants of Concern (VOC) and endemic human coronaviruses (HCoVs), and additionally by three commercial SARS-CoV-2 antibody assays.ResultsOverall, 33.76% of SARS-CoV-2 exposed children and 57.88% adults were seropositive. Children were five times more likely to have seroconverted without symptoms compared to adults. Despite the frequently asymptomatic course of infection, children had higher specific antibody levels, and their antibodies persisted longer than in adults (96.22% versus 82.89% still seropositive 11-12 months post infection). Of note, symptomatic and asymptomatic infections induced similar humoral responses in all age groups. In symptomatic children, only dysgeusia was found as diagnostic indicator of COVID-19. SARS-CoV-2 infections occurred independent of HCoV serostatus. Antibody binding responses to VOCs were similar in children and adults, with reduced binding for the Beta variant in both groups.ConclusionsThe long-term humoral immune response to SARS-CoV-2 infection in children is robust and may provide long-term protection even after asymptomatic infection.(Study ID at German Clinical Trials Register: 00021521)

Zika virus (ZIKV) causes severe birth defects and can be transmitted via sexual intercourse. Semen from ZIKV-infected individuals contains high viral loads and may therefore serve as an important vector for virus transmission. Here we analyze the effect of semen on ZIKV infection of cells and tissues derived from the anogenital region. ZIKV replicates in all analyzed cell lines, primary cells, and endometrial or vaginal tissues. However, in the presence of semen, infection by ZIKV and other flaviviruses is potently inhibited. We show that semen prevents ZIKV attachment to target cells, and that an extracellular vesicle preparation from semen is responsible for this anti-ZIKV activity. Our findings suggest that ZIKV transmission is limited by semen. As such, semen appears to serve as a protector against sexual ZIKV transmission, despite the availability of highly susceptible cells in the anogenital tract and high viral loads in this bodily fluid., Semen from Zika virus infected individuals can contain high viral loads and can result in sexual transmission. Here, Müller et al. show that semen, and particularly seminal preparations containing extracellular vesicles, inhibit infection of Zika and other flaviviruses.

The human cytomegalovirus (HCMV) tegument protein pUL71 is required for efficient secondary envelopment and accumulates at the Golgi compartment-derived viral assembly complex (vAC) during infection. Analysis of various C-terminally truncated pUL71 proteins fused to enhanced green fluorescent protein (eGFP) identified amino acids 23 to 34 as important determinants for its Golgi complex localization. Sequence analysis and mutational verification revealed the presence of an N-terminal tyrosine-based trafficking motif (YXXΦ) in pUL71. This led us to hypothesize a requirement of the YXXΦ motif for the function of pUL71 in infection. Mutation of both the tyrosine residue and the entire YXXΦ motif resulted in an altered distribution of mutant pUL71 at the plasma membrane and in the cytoplasm during infection. Both YXXΦ mutant viruses exhibited similarly decreased focal growth and reduced virus yields in supernatants. Ultrastructurally, mutant-virus-infected cells exhibited impaired secondary envelopment manifested by accumulations of capsids undergoing an envelopment process. Additionally, clusters of capsid accumulations surrounding the vAC were observed, similar to the ultrastructural phenotype of a UL71-deficient mutant. The importance of endocytosis and thus the YXXΦ motif for targeting pUL71 to the Golgi complex was further demonstrated when clathrin-mediated endocytosis was inhibited either by coexpression of the C-terminal part of cellular AP180 (AP180-C) or by treatment with methyl-β-cyclodextrin. Both conditions resulted in a plasma membrane accumulation of pUL71. Altogether, these data reveal the presence of a functional N-terminal endocytosis motif that is an important determinant for intracellular localization of pUL71 and that is furthermore required for the function of pUL71 during secondary envelopment of HCMV capsids at the vAC. IMPORTANCE Human cytomegalovirus (HCMV) is the leading cause of birth defects among congenital virus infections and can lead to life-threatening infections in immunocompromised hosts. Current antiviral treatments target viral genome replication and are increasingly overcome by viral mutations. Therefore, identifying new targets for antiviral therapy is important for future development of novel treatment options. A detailed molecular understanding of the complex virus morphogenesis will identify potential viral as well as cellular targets for antiviral intervention. Secondary envelopment is an important viral process through which infectious virus particles are generated and which involves the action of several viral proteins, such as tegument protein pUL71. Targeting of pUL71 to the site of secondary envelopment appears to be crucial for its function during this process and is regulated by utilizing host trafficking mechanisms that are commonly exploited by viral glycoproteins. Thus, intracellular trafficking, if targeted, might present a novel target for antiviral therapy.