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Hantaviruses constitute a genus of hemorrhagic fever viruses in the family Bunyaviridae. Huiskonen et al. (p. 4889-4897) have studied the structure of Tula hantavirus particles using electron cryotomography. The structure of the membrane glycoprotein spike, at 3.6-nm resolution, reveals a fourfold symmetric assembly. Organization of the spikes on the viral membrane is nonrandom and differs from that of other bunyaviruses studied to date. These new structural findings suggest that specific interactions between the spikes play a major role in the viral budding process.
Human papillomaviruses (HPVs) cause most cervical cancers and replicate their genomes in differentiated epithelial cells. In normal epithelia, these cells have exited the cell cycle, whereas in HPV infections, they retain proliferative capability. Melar-New and Laimins (p. 5212-5221) provide evidence that microRNA 203 (miR-203) is targeted by HPV proteins to allow differentiated cells to reenter S phase. HPV E7 downregulates miR-203 expression in suprabasal cells to maintain high levels of ΔNp63, which is important for differentiation-dependent HPV genome amplification.
Minute virus of mice (MVM) and other parvoviruses replicate more efficiently in transformed cells by mechanisms that are only partly understood. Ventoso et al. (p. 5043-5051) show that protein kinase R (PKR) is activated by the R1 genomic messenger of MVM, leading to eIF2α phosphorylation and inhibition of viral gene expression. Tumor-derived cell lines susceptible to MVM fail to increase PKR-mediated eIF2α phosphorylation in response to infection. Thus, translation control by the PKR/eIF2α system is a major regulatory mechanism of parvovirus oncotropism.
Some human immunodeficiency virus (HIV)-infected individuals produce broadly neutralizing antibody responses against HIV. Pietzsch et al. (p. 5032-5042) dissected the memory B cell response against gp41 in six patients with broadly neutralizing serologic activity. In this study, 131 anti-gp41 antibodies cloned from the anti-gp41-specific memory B cell compartment target six different antigenic clusters on the gp41 ectodomain without significant immunodominance. Although none of the cloned antibodies show neutralizing activity at physiologic concentrations, several were able to neutralize at supraphysiologic levels.
Some vaccines display diminished efficacy in the first few months of life. To overcome this problem with respiratory syncytial virus (RSV), Harker et al. (p. 5294-5302) engineered RSV to express the host cytokine gamma interferon. Infection of neonatal mice with this RSV recombinant caused accelerated macrophage maturation and prevented the immunological “imprinting” that causes immunopathological pulmonary responses elicited by adult rechallenge. In contrast to the effects on ectromelia virus, expression of interleukin-4 did not enhance primary disease but led to Th2 immune programming. Thus, coexpression of cytokines in live vaccines has promise but must be carefully evaluated.