Human chorionic gonadotropin hormone prevents wasting syndrome and death in HIV-1 transgenic mice.

Abstract

At birth, transgenic mice, homozygous for the HIV-1 provirus pNL4-3, deleted in gag/pol, are normal in appearance and weight. Within several days after birth, the pups develop a syndrome characterized by dry, scaly, hyperkeratotic skin, growth failure, and death. The possibility that the homozygous embryos are being protected during gestation by a maternal factor led us to treat the newborn animals with various pregnancy-related hormones including human chorionic gonadotropin (hCG), estrogen, progesterone, and dexamethasone. Treatment with hCG prevented death, led to normal growth, and markedly reduced skin lesions. In contrast to the skin of the untreated homozygous pups, which expressed high levels of HIV mRNA and proteins (i.e., gp120 and Nef), the skin of the hCG-treated pups showed a marked reduction in both HIV mRNA and proteins. Discontinuation of hCG resulted in the reappearance of HIV transcripts and proteins, skin lesions, and growth failure resulting in death. In addition, HIV transcripts and proteins were reduced significantly in heterozygous mothers during pregnancy, but reappeared after parturition. Similarly, hCG treatment resulted in a decrease of HIV proteins in the skin of nonpregnant heterozygous transgenic mice. These findings suggest that the inhibiting effect of hCG on HIV expression may be clinically useful in the treatment of HIV infections, and may be responsible, during pregnancy, for the low transmission of HIV from infected mothers to their offspring. (

Human chorionic gonadotropin is an immune modulator and can prevent autoimmune diabetes in NOD mice

“…Purified hCG and a 400-2,000 Da fraction of clinical grade hCG were shown to prevent diabetes in mice [6]. Another study showed that treatment with hCG prevented the wasting and death of transgenic mice carrying human immunodeficiency virus genes [7]. Recent studies have shown that this wasting syndrome is due in part to high levels of TNF-α, which can be suppressed by treatment with hCG [8].…”

Leukemia inhibitory factor inhibits HIV-1 replication and is upregulated in placentae from nontransmitting women

“…Third, maternal production of HIV-1-specific neutralizing Ab or cytotoxic T lymphocytes may inhibit HIV replication during pregnancy (10,11). Last, expression of soluble factors that inhibit HIV replication has been described previously (12)(13)(14).…”

“…Investigating conditions associated with transmission and nontransmission of HIV-1 from mothers to neonates suggests the presence of HIV-suppressive activity in the placenta. Studies in HIV-1 transgenic mice have demonstrated that the pregnancy-related hormone human chorionic gonadotropin (β-hCG) exerts an HIV-1-inhibitory effect (13). Subsequent studies propose that an unidentified factor associated with β-hCG inhibits HIV-1 replication whereas highly purified preparations of β-hCG demonstrated no HIV-1-inhibitory effects (14).…”

Mother-to-infant transmission of HIV-1: the placenta fights back

“…Thus, whether HIV-1 infection of the placenta decreases production of LIF, making transplacental transmission of virus more likely, or whether the constitutive expression of LIF is lower in some placentas than others, is unclear. De et al have made a similar observation for human chorionic gonadotropin (hCG) (19). In vitro, hCG can suppress HIV-1 reverse transcription in infected lymphocytes and monocytes and can block viral transmission resulting from cell-tocell contact between HIV-1-infected lymphocytes and placental trophoblasts.…”

“…Progesterone promotes the development of T-helper cells that produce Th2 cytokines including IL-4 and IL-10. IL-4 is of particular interest because in vitro it promotes the growth of syncytium-inducing (SI) virus by increasing CXCR4 expression on CD4 + lymphocytes and decreasing CCR5 expression, and by stimulating replication of HIV-1 isolates via transcriptional activation (19). Moreover, recent data suggest that homozygosity of a polymorphism in the IL-4 promoter region, IL-4 589T, is correlated with increased rates of SI variant acquisition in HIV-1-infected individuals (20).…”