The study examines the impact of climate indicators on COVID-19 epidemic in New York City. • Average temperature, minimum temperature and air quality have significant correlation with COVID-19 epidemic. • Currently there is no scientific evidence that warm weather would suppress COVID-19 epidemic.
Genetic variation of human immunodeficiency virus (HIV-1) represents a major obstacle for AIDS vaccine development. To decrease the genetic distances between candidate immunogens and field virus strains, we have designed and synthesized an artificial group M consensus env gene (CON6 gene) to be equidistant from contemporary HIV-1 subtypes and recombinants. This novel envelope gene expresses a glycoprotein that binds soluble CD4, utilizes CCR5 but not CXCR4 as a coreceptor, and mediates HIV-1 entry. Key linear, conformational, and glycan-dependent monoclonal antibody epitopes are preserved in CON6, and the glycoprotein is recognized equally well by sera from individuals infected with different HIV-1 subtypes. When used as a DNA vaccine followed by a recombinant vaccinia virus boost in BALB/c mice, CON6 env gp120 and gp140CF elicited gamma interferon-producing T-cell responses that recognized epitopes within overlapping peptide pools from three HIV-1 Env proteins, CON6, MN (subtype B), and Chn19 (subtype C). Sera from guinea pigs immunized with recombinant CON6 Env gp120 and gp140CF glycoproteins weakly neutralized selected HIV-1 primary isolates. Thus, the computer-generated "consensus" env genes are capable of expressing envelope glycoproteins that retain the structural, functional, and immunogenic properties of wild-type HIV-1 envelopes.The high level of genetic variability of HIV-1 poses a major hurdle for AIDS vaccine development. Genetic differences among HIV-1 groups M, N, and O are extensive, ranging from 30 to 50% in the gag and env genes, respectively (14,20,33,35). HIV-1 also frequently recombines among different subtypes to create circulating recombinant forms (CRFs) and novel recombinants (5, 27, 28). To overcome the challenge of HIV-1 diversity, "centralized" HIV-1 genes have been proposed to use in HIV-1 immunogen design. These strategies include using consensus sequences, the most frequent base found in a given position, or ancestral or center-of-the-tree sequences, both modeled from phylogenetic trees (9,10,12,18,23,24). A sequence that is central to all HIV-1 epidemic strains within group M would increase amino acid similarities with contemporary field HIV-1 isolates relative to intersubtype distances and therefore might be useful in a setting where diverse subtypes and recombinants are cocirculating (12). However, because centralized genes are artificially made, it has been of great concern that these genes may not be able to fold into native conformations, perform biological functions of native Env, preserve Env antigenic epitopes, or induce salutary immune responses when used as immunogens. To address these concerns, we synthesized an artificial group M consensus env gene (CON6 gene) and studied its biological, antigenic, and immunological properties. Our studies demonstrated that CON6 proteins are biologically functional and are immunogenic for eliciting immune responses to wild-type HIV-1 strains. MATERIALS AND METHODSExpression of CON6 gp120 and gp140CF proteins by using rVVs. To generate s...
In recent months, Covid-19 has caused significant global social and economic distress. Governments and health officials around the world have introduced mandatory preventive measures to combat Covid-19, i.e., hand sanitizers, gloves, and masks, which have contributed to large quantities of medical wastes. Social distancing and mandatory lockdown have also been put in place to protect people from Covid-19. This epidemic has caused severe demographic changes and unemployment, and economic activities have been shut down to save human lives. Transportation and travel industries are most severely hit as global tourism has fallen to almost zero in recent months; as a solution, economic institutes have introduced stimulus packages worth more than $6 trillion. However, restricted economic activities have also contributed towards a cleaner environment. However, environmental changes are not permanent, and the pollution level may rise again in the future. As a result, current research suggests that policymakers must introduce stringent environmental policies to promote clean energy.
The HIV-1 gp41 envelope (Env) membrane proximal external region (MPER) is an important vaccine target that in rare subjects can elicit neutralizing antibodies. One mechanism proposed for rarity of MPER neutralizing antibody generation is lack of reverted unmutated ancestor (putative naive B cell receptor) antibody reactivity with HIV-1 envelope. We have studied the effect of partial deglycosylation under non-denaturing (native) conditions on gp140 Env antigenicity for MPER neutralizing antibodies and their reverted unmutated ancestor antibodies. We found that native deglycosylation of clade B JRFL gp140 as well as group M consensus gp140 Env CON-S selectively increased the reactivity of Env with the broad neutralizing human mAbs, 2F5 and 4E10. Whereas fully glycosylated gp140 Env either did not bind (JRFL), or weakly bound (CON-S), 2F5 and 4E10 reverted unmutated ancestors, natively deglycosylated JRFL and CON-S gp140 Envs did bind well to these putative mimics of naive B cell receptors. These data predict that partially deglycoslated Env would bind better than fully glycosylated Env to gp41-specific naïve B cells with improved immunogenicity. In this regard, immunization of rhesus macaques demonstrated enhanced immunogenicity of the 2F5 MPER epitope on deglyosylated JRFL gp140 compared to glycosylated JRFL gp140. Thus, the lack of 2F5 and 4E10 reverted unmutated ancestor binding to gp140 Env may not always be due to lack of unmutated ancestor antibody reactivity with gp41 peptide epitopes, but rather, may be due to glycan interference of binding of unmutated ancestor antibodies of broad neutralizing mAb to Env gp41.
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