Mymetics Corp (MYMX)

[Work Harder]

Mucosal AIDS virus transmission is enhanced by antiviral IgG isolated early in infection

AIDS: December 1, 2021 - Volume 35 - Issue 15 - p 2423-2432

Methods

Cell lines, reagents and virus
SupT1.R5 cells (CD4+CCR5+CR2+) were provided by J.A. Hoxie (University of Pennsylvania), A3R5.7 cells by D.C. Montefiori (Duke University), SHIV-1157ip [23] gp120 and gp160 by S.L. Hu (University of Washington), mAb Fm-6-IgG1 by W.A. Marasco (Dana-Farber Cancer Institute), and HIV-1MN gp41, consensus-clade C peptides, and CN54 gp140 [24] by the NIH AIDS Reagent Program. We generated reporter virus NL-LucR.1157ipd3N4 by cloning SHIV-1157ipd3N4 [25]env into plasmid pNL-LucR.T2A (provided by C. Ochsenbauer, University of Alabama). SHIV-1157ipd3N4 stock [grown in rhesus macaque peripheral blood mononuclear cells (PBMC)] contained 713 ng/ml of p27 and 7 × 106 50% tissue culture infectious doses (TCID50)/ml (measured in TZM-bl cells).

Intrarectal SHIV-1157ipd3N4 challenge
To test the hypothesis that early-stage anti-HIV Env IgG enhances in-vivo viral acquisition, we performed an end-point virus titration in macaques, using an upfront heterologous, R5 tier 2 clade C SHIV. To avoid confounding influences of different viral quasi-species, we selected an infectious molecular clone, SHIV-1157ipd3N4 [25]. We enrolled two groups of eight macaques. First, we determined minimal infectious and 50% animal infectious doses (AID50) in naive animals, which were sequentially exposed intrarectally to increasingly diluted SHIV stock (Fig. 4). After a given animal's viremia was >104 copies/ml, the next macaque was inoculated with a ten-fold higher virus-stock dilution, until a 1 : 10,000 dilution failed to infect. Subsequent animals were then exposed to intermediate dilutions; animals that remained aviremic on day 28 after initial challenge were re-exposed to a high virus inoculum (1 : 2 dilution of the stock); all such animals became viremic (Fig. 5a).

https://journals.lww.com/aidsonline/Fulltext/2021/12010/Mucosal_AIDS_virus_transmission_is_enhanced_by.2.aspx

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