Two clades of SFTSV may have evolved separately over time. On rare occasions, the viruses were transmitted overseas to the region in which viruses of the other clade were prevalent.

The present data suggest that KD-247 has certain advantages for possible passive immunotherapy. They are: high concentrations of KD-247 are needed for viral acquisition of KD-247 resistance; the escape variants are more sensitive to CCR5 inhibitors and rsCD4; and there are high levels of synergism between KD-247 and CCR5 inhibitors at all concentrations tested.

KD-247, a humanized monoclonal antibody to an epitope of gp120-V3 tip, has potent cross-neutralizing activity against subtype B primary human immunodeficiency virus type 1 (HIV-1) isolates. To assess how KD-247 escape mutants can be generated, we induced escape variants by exposing bulked primary R5 virus, MOKW, to increasing concentrations of KD-247 in vitro. In the presence of relatively low concentrations of KD-247, viruses with two amino acid mutations (R166K/D167N) in V2 expanded, and under high KD-247 pressure, a V3 tip substitution (P313L) emerged in addition to the V2 mutations. However, a virus with a V2 175P mutation dominated during passaging in the absence of KD-247. Using domain swapping analysis, we demonstrated that the V2 mutations and the P313L mutation in V3 contribute to partial and complete resistance phenotypes against KD-247, respectively. To identify the V2 mutation responsible for the resistance to KD-247, we constructed pseudoviruses with single or double amino acid mutations in V2 and measured their sensitivity to neutralization. Interestingly, the neutralization phenotypes were switched, so that amino acid residue 175 (Pro or Leu) located in the center of V2 was exchanged, indicating that the amino acid at position 175 has a crucial role, dramatically changing the Env oligomeric state on the membrane surface and affecting the neutralization phenotype against not only anti-V3 antibody but also recombinant soluble CD4. These data suggested that HIV-1 can escape from anti-V3 antibody attack by changing the conformation of the functional envelope oligomer by acquiring mutations in the V2 region in environments with relatively low antibody concentrations.The envelope protein (Env) of human immunodeficiency virus type 1 (HIV-1) presents on the virus surface as "spikes" composed of trimers comprising three gp120-gp41 complexes (6,32,33). Among the regions that induce the neutralization antibody (NAb) response, the third variable domain (V3 loop) of gp120 is considered one of the major targets of the host immune response (23, 69). It has been estimated that as much as half of the antibody response against HIV-1 Env in patient serum is directed against the V3 region (43). A recent crystallographic study revealed that the V3 loop contains features that are essential for coreceptor binding and that the extended nature and antibody accessibility of V3 are associated with its immunodominance (20).HIV-1 primary isolates are relatively resistant to neutralization by NAbs and recombinant soluble CD4 (rsCD4) compared with variants selected for growth in permanent cell lines (42,52,55). Studies addressing differences between neutralization-sensitive and -resistant variants have revealed the involvement of several mechanisms that underlie the neutralization resistance of primary isolates, including the occlusion of epitopes within the oligomer, extensive glycosylation, and extension of variable loops from the surface of the complex, as well as steric and conformational blocking of receptor binding sites ...

Summary.One hundred and three patients with juvenile-onset Type 1 (insulin-dependent) diabetes mellitus have been studied for evidence of previous Coxsackie B virus infection and compared with age-and sex-matched controls. Coxsackie B4 or B3 neutralization titre > 80 were more common among the patients than among the control subjects, but showed no association with HLA-B phenotypes.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging life-threatening infectious disease caused by the tickborne SFTS virus (SFTSV), first identified in China in 2009 and then in Japan in 2013. Human SFTS cases were reported to be concentrated in western Japan, but the epidemiological conditions of SFTSV infection in a specific region are still obscure. We performed an epidemiological study of SFTSV in Oita Prefecture on the island of Kyushu, located in western Japan. For our research, we collected sera from wild and domestic animals (deer, wild boars, raccoons, cats, and dogs) and ticks from January 2010 to November 2020 in Oita. The anti-SFTSV antibody positivity rate of deer in 2014 was significantly higher than that in 2011 (65% versus 27%, P < 0.001). The anti-SFTSV antibody positivity rates of deer, wild boars, raccoons, wild dogs, domestic dogs, and domestic cats were 55%, 12%, 27%, 1.8%, 0.53%, and 1.4%, respectively. Moreover, RT-PCR could not detect SFTSV in any tick sample. Of the six areas of Oita Prefecture, only the Eastern area showed no incidence or possibility of SFTSV infection among wild and domestic animals, ticks, and human beings. Further investigation is required to assess whether local seroepidemiology in animals will help assess the risk of SFTSV infections in inhabitants.