In previous studies, we demonstrated that single-chain variable fragments (scFvs) from anti-human immunodeficiency virus (HIV) Env monoclonal antibodies act as entry inhibitors when tethered to the surface of target cells by a glycosyl-phosphatidylinositol (GPI) anchor. Interestingly, even if a virus escapes inhibition at entry, its replication is ultimately controlled. We hypothesized that in addition to functioning as entry inhibitors, anti-HIV GPI-scFvs may also interact with Env in an infected cell, thereby interfering with the infectivity of newly produced virions. Here, we show that expression of the anti-HIV Env GPI-scFvs in virus-producing cells reduced the release of HIV from cells 5- to 22-fold, and infectivity of the virions that were released was inhibited by 74% to 99%. Additionally, anti-HIV Env GPI-scFv X5 inhibited virion production and infectivity after latency reactivation and blocked transmitter/founder virus production and infectivity in primary CD4 T cells. In contrast, simian immunodeficiency virus (SIV) production and infectivity were not affected by the anti-HIV Env GPI-scFvs. Loss of infectivity of HIV was associated with a reduction in the amount of virion-associated Env gp120. Interestingly, an analysis of Env expression in cell lysates demonstrated that the anti-Env GPI-scFvs interfered with processing of Env gp160 precursors in cells. These data indicate that GPI-scFvs can inhibit Env processing and function, thereby restricting production and infectivity of newly synthesized HIV. Anti-Env GPI-scFvs therefore appear to be unique anti-HIV molecules as they derive their potent inhibitory activity by interfering with both early (receptor binding/entry) and late (Env processing and incorporation into virions) stages of the HIV life cycle. The restoration of immune function and persistence of CD4 T cells in HIV-1-infected individuals without antiretroviral therapy requires a way to increase resistance of CD4 T cells to infection by both R5- and X4-tropic HIV-1. Previously, we reported that anchoring anti-HIV-1 single-chain variable fragments (scFvs) via glycosyl-phosphatidylinositol (GPI) to the surface of permissive cells conferred a high level of resistance to HIV-1 variants at the level of entry. Here, we report that anti-HIV GPI-scFvs also derive their potent antiviral activity in part by blocking HIV production and Env processing, which consequently inhibits viral infectivity even in primary infection models. Thus, we conclude that GPI-anchored anti-HIV scFvs derive their potent blocking activity of HIV replication by interfering with successive stages of the viral life cycle. They may be effectively used in genetic intervention of HIV-1 infection.

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In 2006, Brittany Mostiller was a 22-year-old mother of two living in poverty in Chicago. When she found out that she was pregnant, she knew immediately that she did not want another child at that time and thought she would be able to use her Medicaid insurance to cover the cost of an abortion. However, Illinois Medicaid did not cover elective abortions at that time, and Ms. Mostiller was unable to come up with the funds on her own. She therefore had no choice but to continue her pregnancy and raise another child, pushing her further into poverty. Ms. Mostiller reported suffering "mentally, emotionally, physically, [and] financially" because she was forced to have a child against her wishes. 1 Is this outcome ethically acceptable?In 1973, abortion was legalized in the United States following the landmark US Supreme Court ruling in Roe v. Wade. 2 With more than 860,000 abortions obtained by US women every year, insurance coverage of abortion procedures is an important issue affecting a significant proportion of the population. 3 In 2011, 45% of all US pregnancies were unintended and about 40% of these ended in elective abortion. 4 Data from 2014 showed that 75% of abortion recipients were poor or low-income and 49% lived below the federal poverty level. 5 Despite these economic hardships, 53% of 2014 abortion patients paid for their abortion out of pocket. 6 In 2014, the 1 McDonough, K. (2017, May 1). Neither of these women wanted to be pregnant. Only one could get an abortion. https://splin terne ws.com/neith er-of-these -women -wante d-to-be-pregn ant-only-one-17946 68225 2 American Civil Liberties Union. (2019). Access denied: Origins of the Hyde Amendment and other restrictions on public funding for abortion. https://www.aclu.org/other/ acces s-denie d-origi ns-hyde-amend ment-and-other -restr ictio ns-publi c-fundi ng-abortion 3 Guttmacher Institute. (2019). Induced abortion in the United States. https://www.guttm acher.org/fact-sheet/ induc ed-abort ion-unite d-states 4 Ibid. 5 Ibid.