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Background: Since the beginning of 2024, several European countries reported unusually high numbers of Human parvovirus B19 (B19V) infections. An increase in B19V incidence rate might have implications for blood products for direct transfusion, however, large data sets for analysis of this outbreak are missing., Study Design and Methods: B19V nucleic acid testing (NAT) of plasma donations collected between June 2018 and May 2024 from mainly Central European countries (n = 9.6 million) and the United States (n = 70.7 million) was done to the individual donation level., Results: In Central Europe, there was a marked increase in B19V incidence from November 2023 onwards, which peaked in April 2024 with a 33-fold higher than average B19V incidence versus before the COVID-19 pandemic. In the United States, a similar trend was seen, with a yet still 6-fold lower increase than in Europe at the same time. The largest increase in B19V positivity was seen in the youngest plasma donor cohort., Discussion: A B19V infection gap during the COVID-19 pandemic is likely the basis for the rebound outbreak in 2023/2024, particularly in Europe. B19V NAT of millions of plasma donations provides for large scale numbers to solidify available epidemiology insight, and to support adequate risk assessments. Based on the situation it may be prudent to consider B19V NAT for blood components specifically directed towards transfusion to higher risk recipients, or alternatively, preselecting B19V seropositive individuals or advanced age donors at higher likelihood of seropositivity and thus lower risk of virus transmission., (© 2024 The Author(s). Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

The 2020 SARS-CoV-2 pandemic is caused by a zoonotic coronavirus transmitted to humans, similar to earlier events. Whether the other, seasonally circulating coronaviruses induce cross-reactive, potentially even cross-neutralizing, antibodies to the new species in humans is unclear. The question is particularly relevant for people with immune deficiencies, as their health depends on treatment with immunoglobulin preparations that need to contain neutralizing antibodies against the pathogens in their environment. Testing 54 intravenous immunoglobulin preparations, produced from plasma collected in Europe and the United States, confirmed highly potent neutralization of a seasonal coronavirus; however, no cross-neutralization of the new SARS-CoV-2 was seen., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Human parvovirus B19 (B19V) is a highly prevalent pathogen, and plasma pools for manufacturing of plasma-derived products have been shown to contain antibodies against B19V (B19V immunoglobulin G [IgG])., Study Design and Methods: The megakaryoblastic cell line UT7/Epo-S1 can be infected with B19V Genotype 1 and as demonstrated here by immunocytochemistry, Western blot, and reverse transcription-polymerase chain reaction (RT-PCR) of B19V-specific mRNA, also with the more recently discovered Genotype 2. Based on B19V RT-PCR analysis of infected UT7/Epo-S1 cells, an infectivity assay was established and implemented for a B19V neutralization assay. To investigate the role of B19V neutralization in relation to B19V IgG titers, more than 1,000 manufacturing plasma pools were tested by enzyme-linked immunosorbent assay., Results: Plasma pools were found to contain a mean B19V IgG titer of 33 +/- 9 IU per mL, with the lowest titer at 11 IU per mL. These 11 IU per mL B19V IgG neutralized 4.6 log B19V Genotype 1 and greater than 3.9 log Genotype 2 infectivity. Accordingly, a 10 percent intravenous immunoglobulin (IVIG) product prepared from such pools was found to contain an even higher B19V neutralization capacity., Conclusion: A high capacity of B19V Genotypes 1 and 2 neutralization was demonstrated in plasma pools for fractionation, an inherent feature based on the constantly high titer of B19V IgG in these pools. The neutralizing activity of B19V IgG was shown to be maintained in the 10 percent IVIG product tested.

The human parvovirus B19 is now divided into three genotypes: type 1 (prototype), type 2 (A6- and LaLi-like), and type 3 (V9-like). In overall DNA sequence, the three virus types differ by approximately 10%. The most striking DNA dissimilarity, of >20%, is observed within the p6 promoter region. Because of the scarcity of data on the biological activities and pathogenetic potentials of virus types 2 and 3, we examined the functional characteristics of these virus types. We found the activities of the three p6 promoters to be of equal strength and to be most active in B19-permissive cells. Virus type 2 capsid protein VP2, alone or together with VP1, was expressed with the baculovirus system and was shown to assemble into icosahedral parvovirus-like particles, which were reactive in the hemagglutination assay. Furthermore, sera containing DNA of any of the three B19 types were shown to hemagglutinate. The infectivities of these sera were examined in two B19-permissive cell lines. Reverse transcription-PCR revealed synthesis of spliced B19 mRNAs, and immunofluorescence verified the production of NS and VP proteins in the infected cells. All three genotypes showed similar functional characteristics in all experiments performed, showing that the three virus types indeed belong to the same species, i.e., human parvovirus B19. Additionally, the antibody activity in sera from B19 type 1- or type 2-infected subjects (long-term immunity) was examined with homo- and heterologous virus-like particles. Cross-reactivity of 100% was observed, indicating that the two B19 genotypes comprise a single serotype.

The human immunodeficiency virus type 1 (HIV-1) Vif protein is specifically packaged into virus particles through an interaction with viral genomic RNA in which it associates with the viral nucleoprotein complex. We now demonstrate for the first time that virus-associated Vif is subject to proteolytic processing by the viral protease (Pr). Pr-dependent processing of Vif was observed both in vivo and in vitro. In vivo processing of Vif was cell type independent and evident by the appearance of a 7-kDa processing product, which was restricted to cell-free virus preparations. Processing of Vif required an active viral Pr and was sensitive to Pr inhibitors such as ritonavir. The processing site in Vif was characterized both in vivo and in vitro and mapped to Ala(150). Interestingly, the Vif processing site is located in a domain that is highly conserved among HIV-1, HIV-2, and simian immunodeficiency virus Vif isolates. Mutations at or near the processing site did not affect protein stability or packaging efficiency but had dramatic effects on Vif processing. In general, mutations that markedly increased or decreased the sensitivity of Vif to proteolytic processing severely impaired or completely abolished Vif function. In contrast, mutations at the same site that had little or no effect on processing efficiency also did not influence Vif function. None of the mutants affected the ability of the virus to replicate in permissive cell lines. Our data suggest that mutations in Vif that cause a profound change in the sensitivity to Pr-dependent processing also severely impaired Vif function, suggesting that intravirion processing of Vif is important for the production of infectious viruses.

The human immunodeficiency virus type 1 (HIV-1) Vif protein plays a critical role in the production of infectious virions. Previous studies have demonstrated the presence of small amounts of Vif in virus particles. However, Vif packaging was assumed to be nonspecific, and its functional significance has been questioned. We now report that packaging of Vif is dependent on the packaging of viral genomic RNA in both permissive and restrictive HIV-1 target cells. Mutations in the nucleocapsid zinc finger domains that abrogate packaging of viral genomic RNA abolished packaging of Vif. Additionally, an RNA packaging-defective virus exhibited significantly reduced packaging of Vif. Finally, deletion of a putative RNA-interacting domain in Vif abolished packaging of Vif into virions. Virion-associated Vif was resistant to detergent extraction and copurified with components of the viral nucleoprotein complex and functional reverse transcription complexes. Thus, Vif is specifically packaged into virions as a component of the viral nucleoprotein complex. Our data suggest that the specific association of Vif with the viral nucleoprotein complex might be functionally significant and could be a critical requirement for infectivity of viruses produced from restrictive host cells.

In addition to its role in receptor binding, the envelope glycoprotein of certain human immunodeficiency virus type 2 (HIV-2) isolates, including ROD10, exhibits a biological activity that enhances the release of HIV-2, HIV-1, and simian immunodeficiency virus particles from infected cells. The present study aims at better defining the functional domains involved in this biological activity. To this end, we have characterized the envelope protein of the ROD14 isolate of HIV-2, which, despite 95% homology with the ROD10 envelope at the amino acid level, is unable to enhance viral particle release. Site-directed mutagenesis showed that the presence of a truncation in the cytoplasmic tail of the ROD14 envelope was not responsible for the lack of activity, as previously reported for the HIV-2 ST isolate (G. D. Ritter, Jr., G. Yamshchikov, S. J. Cohen, and M. J. Mulligan, J. Virol. 70:2669-2673, 1996). Similarly, several modifications of the length of the ROD10 envelope cytoplasmic tail did not impair its ability to enhance particle release, suggesting that, in the case of the HIV-2 ROD isolate, particle release activity is not regulated by the length of the cytoplasmic tail.

In this study, we present the first detection of a focus of tick-borne encephalitis (TBE) virus-infected ticks in Liechtenstein. The focus is located on a much-used forest path near Vaduz, the capital of the principality. The virus isolated is a representative of the Western subtype of the TBE virus. It is thus closely related to or identical with the other strains isolated in western Europe.

There have been a few severe cases of tick-borne encephalitis in Liechtenstein during the last 20 years. To form a better idea of the risk of infection and the potential benefit of vaccination, a total of 311 sera from different cohorts were investigated for antibodies to tick-borne encephalitis. The mean seroprevalence found was 3.6% and was not higher even in persons who were active in professional forestry. The antibodies measured derived in all groups mainly from previous vaccination and in only 2 cases (0.6%) from natural infection. It is concluded that the risk of TbE infection in Liechtenstein is very low. Therefore, a reduction in cases would probably be achieved only by mass vaccination.