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Intracellular lipid droplets (LDs) can accumulate in response to inflammation, metabolic stresses, and other physiological/pathological processes. Herein, we investigated whether spike proteins of SARS-CoV-2 induce LDs in human peripheral blood mononuclear cells (PBMCs) and in pulmonary microvascular endothelial cells (HPMECs). PBMCs or HPMECs were incubated alone or with endotoxin-free recombinant variants of trimeric spike glycoproteins (Alpha, Beta, Delta, and Omicron, 12 µg/mL). Afterward, cells were stained with Oil Red O for LDs, cytokine release was determined through ELISA, and the gene expression was analyzed through real-time PCR using TaqMan assays. Our data show that spikes induce LDs in PBMCs but not in HPMECs. In line with this, in PBMCs, spike proteins lower the expression of genes involving lipid metabolism and LD formation, such as SREBF1, HMGCS1, LDLR, and CD36. On the other hand, PBMCs exposed to spikes for 6 or 18 h did not increase in IL-1β, IL-6, IL-8, MCP-1, and TNFα release or expression as compared to non-treated controls. Thus, spike-induced LD formation in PBMCs seems to not be related to cell inflammatory activation. Further detailed studies are warranted to investigate in which specific immune cells spikes induce LDs, and what are the pathophysiological mechanisms and consequences of this induction in vivo. [ABSTRACT FROM AUTHOR]

Virtually all the major advances against viral disease have come in the form of preventive immunization rather than a cure. Although research continues for effective treatments for AIDS, the greatest long-term hope lies in prevention. Unfortunately, the AIDS virus has not proved as amenable to vaccine development as have viruses like smallpox and polio. However, researchers have now demonstrated that an experimental vaccine can protect chimpanzees against infection with the AIDS virus. Two experimental vaccines were evaluated, one based upon the viral envelope protein gp120, and the other on the gp160 protein. The proteins were prepared by recombinant DNA technology, and therefore the vaccines contained no trace of actual viruses. The adjuvant, which is an additional material designed to stimulate the immune response to a vaccine, was aluminum hydroxide. This is significant, since aluminum hydroxide is already approved for use in humans. The investigators found that immunization with gp120 protected the chimpanzees against infection when they were later injected with the AIDS virus. The immunization with gp160 was ineffective, and when these animals were injected with HIV-1, they developed infections within seven weeks. However, it is uncertain that humans will have the same protective antibody response as the chimpanzees. Furthermore, for a vaccine to be practical in humans, the immunity must be long-lasting. In addition, there are numerous varieties of the AIDS virus in the human population, and it is uncertain that a single vaccine can provide protection against them all. Nevertheless, it is significant that protective immunity can be achieved using only protein molecules produced by molecular biology. This may eliminate the problems of using live attenuated virus as a vaccine, and should speed up the development and approval process for an AIDS vaccine. (Consumer Summary produced by Reliance Medical Information, Inc.)

Genes that code for CD4 and for an immunoglobulin molecule (IgG) were fused to form CD4 immunoadhesin, which has properties of both molecules. CD4 is a membrane protein on T lymphocytes (a type of white blood cell) that is the receptor for human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS). It can be isolated from the membrane and in that form is called soluble (not attached to a cell) CD4. It binds to the HIV protein gp120 and blocks HIV from binding and infecting T lymphocytes; it also has a long half-life in the blood plasma. Like the IgG molecule, CD4 immunoadhesin binds with a cellular receptor known as the Fc receptor. CD4 immunoadhesin can mediate the killing of HIV cells, an action known as antibody-dependent cell-mediated cellular cytotoxicity (ADCC). However, it does not mediate ADCC against cells containing the CD4 receptor with gp120 when these cells are not infected. This change is important because in AIDS patients, ADCC causes the death of cells that express CD4; CD4 would otherwise be involved in an immune response against the virus. In primates, CD4 immunoadhesin (like IgG) can cross the placenta and provide protection to the unborn fetus. CD4 immunoadhesins may be developed for therapeutic use, especially in preventing the transmission of HIV infection from the mother to the fetus. (Consumer Summary produced by Reliance Medical Information, Inc.)