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We aimed to investigate whether the sequence length of HIV-1 increases over time. We performed a longitudinal analysis of full-length coding region sequences (FLs) during an HIV-1 outbreak among patients with hemophilia and local controls infected with the Korean subclade B of HIV-1 (KSB). Genes were amplified by overlapping RT-PCR or nested PCR and subjected to direct sequencing. Overall, 141 FLs were sequentially determined over 30 years in 62 KSB-infected patients. Phylogenetic analysis indicated that within KSB, two FLs from plasma donors O and P comprised two clusters, together with 8 and 12 patients with hemophilia, respectively. Signature pattern analysis of the KSB of HIV-1 revealed 91 signature nucleotide residues (1.1%). In total, 48 and 43 signature nucleotides originated from clusters O and P, respectively. Six positions contained 100% specific nucleotide(s) in clusters O and P. In-depth FL analysis for over 30 years indicated that the KSB FL significantly increased over time before combination antiretroviral therapy (cART) and decreased with cART. This increase occurred due to the significant increase in env and nef genes, originating in the variable regions of both genes. The increase in sequence length of HIV-1 over time suggests an evolutionary direction. [ABSTRACT FROM AUTHOR]

We determined the earliest full-length HIV-1 gag gene sequences in 110 patients with HIV-1, including 20 hemophiliacs (HPs) and 90 local controls (LCs). The gag gene from stored sera was amplified using RT-PCR, and was subjected to direct sequencing. Phylogenetic analysis indicated that 94 and 16 sequences belonged to the Korean subclade of HIV-1 subtype B (KSB) and subtype B, respectively. A total of 12 signature pattern amino acids were found within the KSB, distinct from the worldwide consensus of subtype B. Within the KSB, the gag gene sequences from donors O and P and those from the 20 HPs comprised two subclusters. In particular, sequences from donor O strongly clustered with those of eight HPs. Moreover, signature pattern analysis indicated that 14 signature nucleotides were shared between the HPs and LCs within KSB (p < 0.01). Among the 14 nucleotides, positions 9 and 5 belonged to clusters O and P, respectively. In conclusion, signature pattern analysis for the gag gene revealed 12 signature pattern residues within the KSB and also confirmed the previous conclusion that the 20 HPs were infected with viruses due to incompletely inactivated clotting factor IX. This study is the first genetic analysis of the HIV-1 gag gene in Korea. [ABSTRACT FROM AUTHOR]

Abstract: We have investigated the adjuvant roles of common herbal medicines (ginseng, Salviae) and their effects on early immune responses during influenza virus infection in a mouse model. Intranasal co-administration with inactivated influenza virus A (PR8) and ginseng or Salviae extract increased the levels of influenza virus specific antibodies and neutralizing activities compared to immunization with PR8 alone, and provided protective immunity. Salviae co-administration significantly enhanced IFN-γ and IL-2 cytokine producing splenocytes while ginseng induced high levels of IL-4 and IL-5 cytokine producing cells after challenge infection. Cells expressing an early activation marker CD69 and levels of a pro-inflammatory cytokine IL-6 were highly elevated in lungs from naïve mice during challenge virus infection, which might be a mechanism in lung inflammation leading to death. In contrast, immunized mice that were co-administered ginseng or Salviae modulated CD69 expressing immune cells, did not produce IL-6, and showed significant enhancement of influenza virus specific IgA antibody in lungs after challenge virus infection. Therefore, these results indicate that both ginseng and Salviae play a role as mucosal adjuvants against influenza virus as well as immuno-modulators during influenza virus infection. [Copyright &y& Elsevier]

Advanced gastric cancer cannot be treated with surgery or conventional cancer therapy, which has prompted a search for new therapeutic modalities. Previously, we and other groups showed that E1B 55 kDa-deleted recombinant adenoviruses, such as YKL-1, effectively replicate and induce cytotoxicity in p53-deficient cancer cells while sparing normal cells. Here, we investigated selective YKL-1 replication and resultant cytolysis in human gastric cancer cells. The cytopathic effects were obvious in all five gastric cancer cell lines we examined. Evaluation of p53 expression indicated that only the AGS cell line retained functionally normal p53. Nevertheless, AGS was 10-fold more sensitive to YKL-1 than the other cell lines. Transmission electron microscopy showed typical morphological alterations along with efficient replication of YKL-1 in AGS cells. Therefore, YKL-1 induces preferential cytotoxic effects in human gastric cancer cells in a p53-independent manner, making YKL-1 a promising therapeutic agent for human gastric cancers. [Copyright &y& Elsevier]

The assessment of the biological activity of capsaicin, the compound responsible for the spicy flavor of chili pepper, produced controversial results, showing either carcinogenicity or cancer prevention. The innate immune system plays a pivotal role in cancer pathology and prevention; yet, the effect of capsaicin on natural killer (NK) cells, which function in cancer surveillance, is unclear. The present study found that capsaicin inhibited NK cell-mediated cytotoxicity and cytokine production (IFN-γ and TNF-α). Capsaicin impaired the cytotoxicity of NK cells, thereby inhibiting lysis of standard target cells and gastric cancer cells by modulating calcium mobilization in NK cells. Capsaicin also induced apoptosis in gastric cancer cells, but that effect required higher concentrations and longer exposure times than those required to trigger NK cell dysfunction. Furthermore, capsaicin inhibited the cytotoxicity of isolated NK cells and of an NK cell line, suggesting a direct effect on NK cells. Antagonists of transient receptor potential vanilloid subfamily number 1 (TRPV1), a cognate capsaicin receptor, or deficiency in TRPV1 expression failed to prevent the defects induced by capsaicin in NK cells expressing functional TRPV1. Thus, the mechanism of action of capsaicin on NK cells is largely independent of TRPV1. Taken together, capsaicin may have chemotherapeutic potential but may impair NK cell function, which plays a central role in tumor surveillance. [ABSTRACT FROM PUBLISHER]