Immune reconstitution prevents continuous equine infectious anemia virus replication in an Arabian foal with severe combined immunodeficiency: lessons for control of lentiviruses

Abstract

Acute infection with equine infectious anemia virus (EIAV), a lentivirus of horses, results in a persistent high-level viremia in Arabian foals affected with severe combined immunodeficiency (SCID). This observation argues against the idea that the transient nature of acute lentiviral viremia is solely a function of viral population dynamics. To extend these studies, EIAV-specific immune reconstitution was attempted prior to EIAV challenge in two SCID foals, using adoptively transferred virus-stimulated lymphocytes derived from persistently EIAV-infected half sibling donors. Following transfer, lymphocyte engraftment occurred in one foal, and EIAV-specific cytotoxic T lymphocytes as well as neutralizing antibody activity developed. Following a brief period of plasma viremia in this foal, EIAV replication was controlled and plasma virus could not be detected by RT-PCR or culture. These results provide further direct evidence that a specific immune response is required for termination of plasma viremia in acute lentiviral infections.

Fig. 1

Experimental time line. DPI = days post-EIAV inoculation

Fig. 2

EIAV-specific RT-PCR products derived from SCID1 (a) and SCID2 (b) plasma, and analyzed by electrophoresis through a 2% agarose gel. Pre = pre-EIAV inoculation. Lanes designated “+” indicate products from reactions containing reverse transcriptase, while lanes designated “-” indicate products from reactions without reverse transcriptase. Gel image obtained using the AlphaImager 2000 digital imaging system (Alpha Innotech Corp., USA)

Fig. 3

(a) CTLe activity in SCID1 PBMC against EIAV-infected homologous (closed circles) and heterologous (open circles) equine kidney (EK) cell targets. Effector:target cell ratio was 20:1. Error bars are standard error. (b) Frequency of EIAV-specific CTLe in SCID1 PBMC, as determined by limiting dilution analysis. Error bars indicate 95% confidence interval.

Fig. 4

(a) Platelet counts/μl for SCID1 (closed circles) and SCID2 (open circles). The horizontal line indicates the low-range normal platelet count for uninfected Arabian SCID foals (151,000/μl). DPI = days post-EIAV inoculation. (b) Packed cell volume (PCV) % for SCID1 (closed circles) and SCID2 (open circles). The horizontal line indicates the low-range normal PCV for 2-month-old uninfected Arabian SCID foals (25%).

Fig. 5

(a) Photomicrograph of a SCID2 lymph node section, lacking follicles and lymphocytes. Bar, 100 μm. (b) Photomicrograph of a SCID1 lymph node section, fully populated with lymphocytes. Bar, 100 μm. (c) Photomicrograph of a SCID1 heart section containing a focus of myocardial necrosis with lymphocyte infiltrates. Bar, 10μm. (d) Photomicrograph of macrophages labeled by immunohistochemistry (dark-staining cells) in a SCID1 spleen section. Bar, 10μm.