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. 1998 Feb;72(2):1600-5.
doi: 10.1128/JVI.72.2.1600-1605.1998.

CD4+-T-cell and CD20+-B-cell changes predict rapid disease progression after simian-human immunodeficiency virus infection in macaques

K K Steger  1 , M Dykhuizen, J L Mitchen, P W Hinds, B L Preuninger, M Wallace, J Thomson, D C Montefiori, Y Lu, C D Pauza
Affiliations

CD4+-T-cell and CD20+-B-cell changes predict rapid disease progression after simian-human immunodeficiency virus infection in macaques

K K Steger et al. J Virol. 1998 Feb.

Abstract

Simian-human immunodeficiency virus 89.6PD (SHIV89.6PD) was pathogenic after intrarectal inoculation of rhesus macaques. Infection was achieved with a minimum of 2,500 tissue culture infectious doses of cell-free virus stock, and there was no evidence for transient viremia in animals receiving subinfectious doses by the intrarectal route. Some animals experienced rapid progression of disease characterized by loss of greater than 90% of circulating CD4+ T cells, sustained decreases in CD20+ B cells, failure to elicit virus-binding antibodies in plasma, and high levels of antigenemia. Slower-progressing animals had moderate but varying losses of CD4+ T cells; showed increases in circulating CD20+ B cells; mounted vigorous responses to antibodies in plasma, including neutralizing antibodies; and had low or undetectable levels of antigenemia. Rapid progression led to death within 30 weeks after intrarectal inoculation. Plasma antigenemia at 2 weeks after inoculation (P < or = 0.002), B- and T-cell losses (P < or = 0.013), and failure to seroconvert (P < or = 0.005) were correlated statistically with rapid progression. Correlations were evident by 2 to 4 weeks after intrarectal SHIV inoculation, indicating that early events in the host-pathogen interaction determined the clinical outcome.

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Figures

FIG. 1
FIG. 1
Changes in the number of circulating CD4+ T cells. The percentages of CD4+ T cells remaining for weeks 1 through 24 p.i. were calculated for each animal with the following formulas: percentage of CD4+ T cells remaining (at week x) = 100 + percent change; percent change = 100 × [(number of CD4+ T cells at week x − number of CD4+ T cells at week 0)/(number of CD4+ T cells at week 0)]. Results for five animals with rapid and sustained losses of CD4+ T cells (A) and for five animals with moderate but varying losses of CD4+ T cell (B) are shown.
FIG. 2
FIG. 2
Changes in the number of circulating CD20+ B cells. The percentages of CD20+ B cells remaining for weeks 1 through 24 p.i. were calculated for each animal by using week 0 values as 100%. (A) Percentages of B cells remaining in the five animals with rapid and sustained losses of CD4+ T cells; (B) percentages of B cells remaining in the five animals with moderate and variable losses of CD4+ T cells.
FIG. 3
FIG. 3
Antibody responses in plasma. Macaque sera were tested with an HIV-2 enzyme-linked immunosorbent assay kit for antiviral antibodies. Absorbance values (405 nm) of plasma samples from weeks 0 through 24 p.i. are depicted for each animal. Open symbols represent results with seronegative macaques, and closed symbols represent results with seropositive macaques.
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