Temporal association of interferon-αand p27 core antigen levels in sera of simian immunodeficiency virus infected monkeys

Microbial Pathogenesis 1996; 20: 171–178

Temporal association of interferon-a and p27 core antigen levels in sera of simian immunodeficiency virus infected monkeys Marlyn P. Langford,1,2∗ Drew H. Wyrick,1 James P. Ganley,1 Gary B. Baskin,3 Michael Murphey-Corb,4 Kenneth F. Soike4 and Louis N. Martin4 Departments of 1Ophthalmology and 2Microbiology, Louisiana State University Medical Center, Shreveport, LA and Departments of 3Pathology and 4Microbiology, Tulane Regional Primate Research Center, Tulane University Medical Center, Covington, LA, U.S.A. (Received June 8, 1995; accepted in revised form November 6, 1995)

Langford M. P. (Departments of Ophthalmology and Microbiology, Louisiana State University Medical Center, Shreveport, LA), D. H. Wyrick, J. P. Ganley, G. B. Baskin, M. MurpheyCorb, K. F. Soike and L. N. Martin. Temporal association of interferon-a and p27 core antigen levels in sera of simian immunodeficiency virus infected rhesus monkeys. Microbial Pathogenesis 1996; 20: 171–178. We report the temporal association of interferon (IFN) and p27 core antigen production during experimental simian immunodeficiency virus Delta B670 (SIV) infection in rhesus monkeys. Peak serum IFN-a levels (102.8–5.0U/ml) occurred 10 days post infection (p.i.) and peak p27 levels (3.1–34.4 ng/ml) occurred 10–14 days p.i. Acid-stable IFN-a (101.6–2.5U/ml) was detected 3–5 days before p27 in sera from three monkeys and was detected with p27 (0.06–3.06 ng/ml) in four monkeys during the primary infection. Serum IFN-a and p27 levels became undetectable 24–40 days p.i. Two monkeys remained asymptomatic for SIV after the primary p27 antigenaemia, three monkeys had recrudescent (3–4 months p.i.) acid stable interferonaemias (101–2.5U/ml) with p27 antigenaemias (0.06–2.7 ng/ml) that persisted until death, and two monkeys had acute SIV infections (died Ζ7 months p.i.) with persistent acid-stable interferonaemia (101.6–2.5U/ml) and p27 antigenaemia (6—9 ng/ml). Our results indicate that the detection of acid-stable IFN-a in serum is closely associated with detection of p27 (P=0.0001) and suggest that detection of acid-stable IFN-a and p27 core antigen is indicative of active SIV infection.  1996 Academic Press Limited

Key words: Simian immunodeficiency virus; interferon-a; infection; host defense.

Introduction Interferon (IFN-a) has been detected in sera collected from patients during primary human immunodeficiency virus (HIV) infection, in 8–20% of sera from asymptomatic HIV seropositive patients, and in 29–91% of sera from symptomatic HIV seropositive AIDS patients.1–5 The detection of an “acid-labile” IFN-a in serum of patients at risk for AIDS is a poor prognostic sign.1,2,4 Also, HIV p24 core antigen is usually detected (60%) in symptomatic AIDS patients seropositive for HIV and ∗ Author to whom correspondence should be addressed: Marlyn P. Langford, Ph.D., Department of Ophthalmology, Louisiana State University Medical Center, 1501 Kings Hwy/P.O. Box 33932, Shreveport, LA 71130-3932 U.S.A. 0882–4010/96/030171+08 $18.00/0

 1996 Academic Press Limited

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is considered to be an unfavorable sign in HIV disease.6–10 Notably, HIV p24 core antigen is generally not detected in serum of asymptomatic HIV-seropositive patients,6,7,10 but is usually associated with detection of infectious HIV.8–10 The detection of IFN during SIV infection in monkeys has been noted.11 However, the temporal relationship of IFN with the biphasic SIV p27 core antigenaemia12 during experimental SIV infection has not been investigated. In addition, we wanted to determine the type(s) of IFN produced during SIV infection, since sera from HIV positive patients with AIDS have been reported to contain an “acidlabile” IFN-a,1,2 while HIV infected human leukocytes in vitro has been shown to produce acid-stable IFN-a,13,14 acid-stable and/or acid-labile IFN-a,14,15 or a mixture of acid-stable IFN-a and acid-labile IFN-c.15–17 We present the association of IFN and SIV p27 core antigen production during experimental SIV Delta B670 infections in seven rhesus monkeys and characterize the SIV induced IFNs. The IFN was produced in association with primary and recrudescent/persistent p27 antigenemias during the course of experimental SIV infection. The IFNs were homologous and were shown to be acid-stable IFN-a.

Results Serum levels of SIV p27 and IFN during SIV infection The course of the primary SIV infection (i.e., interferonaemia and p27 antigenaemia 1–4 weeks p.i.) was similar in seven monkeys inoculated with SIV. However, the period of time between the primary and recrudescent SIV p27 antigenaemia varied among the seven monkeys (Fig. 1 A–G). Quiescent SIV infections (i.e., no detectable recrudescent p27 antigenaemia) were observed in two monkeys, K697 (Fig. 1A) and J536 (Fig. 1B). Low levels of p27 (0.33 and 0.08 ng/ml, respectively) were detected 10 days p.i., p27 levels peaked (4.5–6.4 ng/ml) 14 days p.i., and then p27 declined to undetectable levels (93 (8)

Recrud./ Persist. HulFN-a HulFN-c

VSV in SBV in VSV in VSV in VSV in HEp-2 HEp-2 LLCMK RK PPC 40− 240− 640 1,280 60− 120− 320 640 1,280 3,200 300 640

60− 300 120− 640 960 200

IFN∗ Titer after pH2

40− 160−