AEGiS-11IAC: Kinetics of interferon production in macaque lymph nodes during primary SIV infection.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Kinetics of interferon production in macaque lymph nodes during primary SIV infection.

Int Conf AIDS 1996 Jul 7-12; 11:13 (abstract no. We.A.385)
Chakrabarti L, Khatissian E, Tovey M, Cumont MC, Monceaux V, Montagnier L, Bruno Hurtrel B; Unite d'Oncologie Virale, Paris, France. Fax: (1) 40 61 34 65. E-mail: chakra@pasteur.fr.

OBJECTIVE: To investigate the role of interferons in the containment of viral burden seen in primary SIV infection.

METHODS: IFN-alpha and IFN-gamma productions were evaluated in lymphoid organs of 8 rhesus macaques inoculated with SIVmac 251. For each animal, 4 lymph nodes obtained sequentially between day 7 and day 68 post inoculation were analyzed by in situ hybridization with 35 [S] labeled probes.

RESULTS: A peak of IFN-alpha producing cells was detected between day 7 and 14, with a maximum of 40 IFN-alpha + cells/2 mm2. Animals with a higher viral burden demonstrated a higher IFN-alpha production in lymph nodes. This correlation was confirmed by biological dosage of serum IFN-alpha, as the secretion of IFN alpha paralleled that of p27 antigenemia.The number of IFN-gamma producing cells detected in lymph nodes also peaked between day 7 and 14 post-inoculation. In this case, however, the height of the peak did not correlate positively with the viral burden in lymph nodes. To further quantify IFN-gamma in lymph nodes, the production of IFN-gamma mRNA was assessed by competitive RT-PCR. The number of IFN-gamma mRNA copies detected varied from 107 to 109 per 0,25 micrograms RNA. For 6 of the 8 animals, the IFN-gamma copy number was inversely related to the p27 antigenemia. The study was extended to 3 other animals that demonstrated a particularly high viral burden in lymph nodes and a persistent viremia. The data showed an inverse correlation between IFN-gamma production in lymph nodes and antigenemia (p is less than 0.03).

CONCLUSIONS: This study demonstrates that macaques that harbor a high viral burden during primary SIV infection are characterized by high IFN-alpha and low IFN-gamma production in lymph nodes. The defect in IFN-gamma production may reflect an early T cell dysfunction in the animals that are the most susceptible to SIV-induced disease.

Keywords: AEGIS, SIV, Macaca, Lymph Nodes, Macaca mulatta, Interferons, Kinetics, Viremia, In Situ Hybridization, Interferon Type II, Interferon-alpha, T-Lymphocytes, RNA Probes, RNA, Messenger, Interferon-beta, Animal, pharmacokinetics, ICA11

960707
WeA385