Exosomes in Virus Infection

Frontiers in Immunology. 2023 Mar 30; 14: 1154217.

Authors: Peng Y, Yang Y, Li Y, Shi T, Luan Y, Yin C.

Exosomes are messengers of intercellular communication in monolayer vesicles derived from cells. It affects the pathophysiological process of the body in various diseases, such as tumors, inflammation, and infection. It has been confirmed that exosomes are similar to viruses in biogenesis, and exosome cargo is widely involved in many viruses' replication, transmission, and infection. Simultaneously, virus-associated exosomes can promote immune escape and activate the antiviral immune response of the body, which bidirectionally modulates the immune response.

Fig. 1 Timeline of studies on exosomes and viral infections.

Exosomes in HIV

• The generation of exosomes is similar to that of RNA viruses, especially retroviruses. HIV is the first RNA virus to be used for exosome research, and it is also one of the most intensively studied viruses. In 2003, Gould proposed "the Trojan exosome hypothesis." The hypothesis holds that retroviruses use preexisting exosome biogenetic pathways to form infectious particles and share protein targeting and biogenetic pathways with exosome, as well as preexisting exosome uptake pathways to form receptor-independent and Env-independent infection ways to promote viral infection.
• Although exosome can promote the spread of HIV-1 and escape host immunity, it also plays an important role in HIV antiviral immunity. Exosomes in healthy human semen block the transmission of HIV-1 from vaginal epithelial cells to target cells and inhibit HIV-1 from crossing the vaginal epithelial barrier in a trans-well model in vitro. More importantly, after the internalization of seminal exosomes, they exert an antiviral response by blocking the activity of HIV-1 reverse transcriptase and reducing the replication of the viral complex, which has been demonstrated in mice.

Exosomes in HBV

• Exosomes can effectively transmit HBV by providing a biogenetic mechanism, acting as an immune barrier, and enhancing the ability of HBV replication. Exosomes derived from the peripheral blood of CHB patients contain abundant viral components, including HBV-DNA, HBV-RNA, HBsAg, and HBeAg, which can induce active infection in human hepatocytes. It can also be transported to NK cells to inhibit NF-kB and p38 MAPK signaling pathways, leading to their dysfunction that destroys the innate immune response and promotes the process of HBV infection.
• Exosomes not only contain HBV-related viral components but also derive a large number of non-coding RNA. By examining extracellular vesicles secreted by HBV-infected human hepatocytes, it is found that miR-21, miR-192, miR-215, miR-221, and miR-222 directly targeted multiple sequences in the 3'UTR of human IL-21 mRNA.
• Exosomes are involved in the release and transmission of HBV and interact with immune cells to regulate the immune response. Extracellular vesicles secreted by HBV-infected cells are endocytosed by monocytes which play an immunosuppressive role by up-regulating PD-L1 and inhibiting the expression of CD69.

Exosomes in HCV

• HCV-infected hepatocytes can secrete exosomes carrying HCV RNA and protein and transmit the contents to other hepatocytes. Due to the protective effect of exosomes, this transmission route can attenuate the effect of antiviral antibodies to a certain extent, which may provide an effective way for the HCV to escape immunity.
• A variety of miRNAs in exosomes regulate the progression of HCV infection, which has the potential value of developing into antiviral drugs and assisting in the judgment of disease progression.
• In terms of immunity, DCs from patients with persistent HCV infection still exhibit normal phagocytic activity, typical class I, and class II HLA expression, and regular cytokine production, indicating that DCs still exert antiviral immunity during persistent HCV infection. Then CD8+T cells are stimulated by exosome-activated DCs to play a joint role in cellular immunity.

Exosomes are important vectors for virus transmission and play an essential role in promoting viral infection and antiviral immunity. Its comprehensive source of cells and a variety of goods endow the exosomes with heterogeneity, providing plenty of biological functions and space for artificial transformation. With the development of isolation and purification technology, researchers' focus has shifted from basic research to clinical application, especially vaccine development. We have reason to believe that exosomes will establish a unique research system in viral diagnosis and treatment.

Creative Bioarray Relevant Recommendations

Exosome Standards

Exosome Research Services

Reference

1. Peng Y, et al. (2023). "Exosome and virus infection." Front Immunol. 14, 1154217.