The rapid time course is consistent with release of pre-formed TNFa protein rather than reflecting de novo cytokine synthesis, post-translational modification, trafficking and externalization, suggesting the predominant influence of vmiR88 and vmiR99 was independent of gene silencing pathways. Additional support for non-RNAi function of the novel vmiR88 and vmiR99 relates to their copy numbers, as host cell miRNAs generally far exceed small RNA reads in HIV infected cells. In general, the RNAi function of miRNA is stoichiometrically dependent, since RNAi translational blockade requires $100 miRNA copies for effective silencing of individual genes by the mechanism of RNAi. However, as HIV-derived vmiR88 and vmiR99 can be released at low copy numbers, the observed biological effects more likely represent activation of alternate pathways that can provide amplification in a signal cascade and stimulate physiologically relevant responses resulting in cytokine release. Detection of abundant Clofentezine vmiR-TAR in HIV-infected cells associated with exosomes in the Pyriproxyfen current study confirms reports by other investigators, and validates our methodology. Although abundant, the observation that vmiR-TAR did not stimulate macrophage TNFa release suggests different regulatory roles for HIV-derived miRNA. VmiR-TAR may influence cellular apoptosis or enhance macrophage susceptibility to HIV infection through targeted gene silencing, although this was not specifically investigated in the current study. Though the current study focused on novel HIV vmiR88 and vmiR99, the potential identification and role of other pro-inflammatory HIV-produced miRNAs cannot be excluded and remains the focus of active investigation. Furthermore, the potential role of other HIV produced miRNAs that may serve an antagonistic or anti-inflammatory role cannot be excluded, and any RNAi influence of novel vmiR88 or vmiR99 cannot be excluded, as these were not specifically investigated in the current study. Snakebites are a serious public health problem in many regions around the world, particularly in tropical and subtropical countries.