A retrovirus belonging to the family of recently discovered human T-cell leukemia viruses (HTLV), but clearly distinct from each previous isolate, has been isolated from a Caucasian patient with signs and symptoms that often precede the acquired immune deficiency syndrome (AIDS). This virus is a typical type-C RNA tumor virus, buds from the cell membrane, prefers magnesium for reverse transcriptase activity, and has an internal antigen (p25) similar to HTLV p24. Antibodies from serum of this patient react with proteins from viruses of the HTLV-I subgroup, but type-specific antisera to HTLV-I do not precipitate proteins of the new isolate. The virus from this patient has been transmitted into cord blood lymphocytes, and the virus produced by these cells is similar to the original isolate. From these studies it is concluded that this virus as well as the previous HTLV isolates belong to a general family of T-lymphotropic retroviruses that are horizontally transmitted in humans and may be involved in several pathological syndromes, including AIDS.

Human hantavirus infections can cause hemorrhagic fever with renal syndrome (HFRS), major signs of the disease being thrombocytopenia and transient kidney dysfunction. By a comprehensive and longitudinal study of circulating B cells, we demonstrate that these two pathologies associate with distinct effects on the humoral immune system during HFRS. Low thrombocyte counts strongly associated with an abnormal frequency of plasmablasts in circulation, whereas kidney dysfunction was indicative of an accumulation of CD27 -B cells and plasmablasts. Finally, we provide evidence that high levels of extracellular ATP in circulation during HFRS correlates with shedding of surface CD27 on B cells via a metallomatrix proteinase-8-mediated mechanism. Since extracellular ATP is known to regulate kidney function, our study reveals a link between kidney dysfunction and the generation of CD27 -IgD -B cells, and a potential molecular target for treatment of the symptomatic phase of HFRS. Dobrava, Seol and Puumala (PUUV) strains, where PUUV is endemic to Scandinavia. To date, no efficacious treatment or vaccination regimen exists to protect against severe hantavirus infections.Well controlled human studies have shown that hantavirus infections cause aberrant activation of both innate and adaptive immunity (5)(6)(7)(8). A potent antiviral IgG-response is associated with protection from severe disease during both HPS and HFRS (9-12) and passive transfer of serum antibodies could reduce case fatality rate in a small cohort of HPS patients (13). These findings clearly demonstrate that activation of the humoral immune system and subsequent elicitation of antiviral antibodies play a central role in the control of viremia and/or pathogenesis during hantavirus infections.A recent study of HPS demonstrated that very high levels of plasmablasts (PBs) and CD27 -IgD -B cells were detected in circulation of patients (14). The rapid and extensive PB-response is similar to that reported during acute dengue virus infection and contrasts to the comparably moderate levels of PBs that are found in circulation during influenza infection or after influenza vaccination (15). An expansion of the CD27 -IgD -B cell subset has previously been shown for numerous inflammatory and infectious diseases, as well as during ageing and cancer (16-21), yet their functional role in humoral immunity remains undetermined. The CD27 -IgD -B cells resemble memory B cells, have isotype switched and hypermutated B cell receptors and therefore likely originate from T cell-dependent germinal center reactions in secondary lymphoid organs (16, 20). In systemic lupus erythematosus (SLE), an expanded population of CD27 -IgD -B cells was associated with the manifestation of nephritis in patients (16). This suggests that their detection in blood may be linked to reduced kidney function, but the cause for their expansion remains to be determined.During HFRS-causing hantavirus infections, reduced kidney function occurs independently of the induced thrombocytopenia (22, 23). We therefor...

How a previous SARS-CoV-2 infection may amplify and model the memory B cell (MBC) response elicited by mRNA vaccines was addressed by a comparative longitudinal study of two cohorts, naive individuals and disease-recovered patients, up to 2 months after vaccination. The quality of the memory response was assessed by analysis of the VDJ repertoire, affinity and neutralization against variants of concerns (VOC), using unbiased cultures of 2452 MBCs. Upon boost, the MBC pool of recovered patients selectively expanded, further matured and harbored potent neutralizers against VOC. Maturation of the MBC response in naive individuals was much less pronounced. Nevertheless, and as opposed to their weaker neutralizing serum response, half of their RBD-specific MBCs displayed high affinity towards multiple VOC and one-third retained neutralizing potency against B.1.351. Thus, repeated vaccine challenges could reduce these differences by recall of affinity-matured MBCs and allow naive vaccinees to cope efficiently with VOC.

Intact and slit nerve fibers of the squid Sepioteuthis sepioidea were incubated in a 50-nM solution of [125I]a-bungarotoxin in artificial seawater, in the absence and in the presence of D-tubocurarine (10 -4 M). The distribution of the radioactive label was then determined by electron microscope autoradiography. It was found that, in the fibers exposed solely to the radioactive toxin, the label was located mainly at the axon-Schwann cell boundary in the intact nerve fibers or at the axonal edge of the Schwann cell layer in the axon-free nerve fiber sheaths. Label was also present in those regions of the Schwann cell layer rich in intercellular channels. No signs of radioactivity were observed in the nerve fibers exposed to the labeled toxin in the presence of i>-tubocurarine. These results indicate that the acetylcholine receptors previously found in the Schwann cell plasma membrane are mainly located over the cell surfaces facing the neighboring axon and the adjacent Schwann cells. These findings represent a further advance in the understanding of the relationships between the axon and its satellite Schwann cell.KEY WORDS Schwann cells acetylcholine receptors squid nerve fiber 9Recent studies carried out on the giant nerve fiber of the tropical squid Sepioteuthis sepioidea (5,6) revealed the presence of acetylcholine receptors in the plasma membrane of the Schwann cell. The external application of acetylcholine (10 -r M) and carbamylcholine (10 -6 M) to the resting nerve fiber causes a long lasting hyperpolarization of the Schwann cells, which can be blocked by the external application of D-tubocurarine (10 -9 M). Eserine (10 -9 M) prolongs the Schwann cell hyperpolarizations produced by acetyicholine (6). It was also found that carbamylcholine increases the relative permeability of the Schwann cell membrane to the potassium ion (6).Further studies carried out on the same nerve fibers (7) permitted the characterization of the sites of action of acetylcholine in the plasma membrane of the Schwann cell. It was found that the c~-toxin derived from the venom of Bungarus multicinctus irreversibly blocks the long-lasting Schwann cell hyperpolarizations after the external application of carbamyicholine to the resting nerve fiber, and that D-tubocurarine protects the Schwann cells against the irreversible action of abungarotoxin (7). In addition, [125I]a-bungarotoxin was found to bind in vitro to the plasma membrane preparations isolated from S. sepioidea peripheral nerves (R. Villegas, F. V. Barnola and J. CELL BIOLOGY 9 The Rockefeller University Press 9 0021-9525/78/0501-037151.00 371on May 12, 2018 jcb.rupress.org Downloaded from

The nonstructural NS1 protein is a virulence factor secreted by dengue virus (DENV)-infected cells. NS1 is known to alter the complement system, activate immune cells and perturb endothelial barriers. Here we show that pro-inflammatory signals are triggered by a high affinity complex formed between NS1 and human high-density lipoproteins (HDL). Electron microscopy images of the NS1-HDL complexes show spherical HDL particles with rod-shaped NS1 protrusions on their surface. These complexes are readily detectable in the plasma of hospitalized dengue patients using anti-apolipoprotein A-I (ApoA-I) antibodies specific of the HDL moiety. The functional reprogramming of HDL particles by the NS1 protein as a means to exacerbate systemic inflammation during DENV infection provides a new paradigm linking the human lipoprotein network to dengue pathogenesis.