Table 1.
Main characteristics of rhesus macaques infected and challenged with LCMV
| Monkey* |
|||||
|---|---|---|---|---|---|
| WE-iv3 | WE-ig7a | WE-ig7b | ARM-iv3 | ARM-ig8 | |
| Primary infection** | |||||
| Outcome | D11 | S | S | S | S |
| Hepatitis | + | − | +/− | − | − |
| Ki-67 | + | − | +/− | − | − |
| IL-6/sTNFRs | + | − | +/− | − | − |
| Viremia | + | − | +/− | − | − |
| IgG ELISA | <2 | <2 | 7.2 | 5.4 | 5.8 |
| PRNT | <1 | <1 | 3.3 | 1.2 | <1 |
| SI | ND | <5 | 25/12 | 13/90 | 7/18 |
| CTL (% Spec. Lysis) | ND | 17/21(10) | 47/64(8) | ND | ND |
| Challenge** | |||||
| Outcome | D14 | S | S | S | |
| Hepatitis | + | − | − | − | |
| Ki-67 | + | − | − | − | |
| IL-6, sTNFRs | + | − | − | − | |
| Viremia | + | − | − | − | |
| IgG ELISA | <2 | 6.0 | 5.2 | 5.3 | |
| PRNT | <1 | 2.0 | 1.9 | <1 | |
| SI | ND | 50/8 | 19/82 | 3/15 | |
| CTL (% Spec. Lysis) | 5/12(6) | 47/44(8) | ND | ND | |
Rhesus macaques were infected with WE or ARM strains of LCMV using intravenous (i.v.) or intragastrical (i.g.) routes. Rhesus WE-iv3 received 1 × 103 PFU of WE strain and died on day 11 after infection. Two monkeys, WE-ig7a and WE-7b, were i.g. inoculated with 1 × 107 PFU of LCMV-WE, and two monkeys, ARM-iv3 and ARM-ig8, were infected with LCMV-ARM, 1 × 103 PFU and 1 × 108 PFU using i.v. and i.g. routes, respectively
“Outcome”, D11, death at day 11 after infection. S, animal survived. “Hepatitis” was evaluated by biochemical liver tests and marked as “+” if liver tests were elevated in be-weekly bleeding samples; “+/−”, transient elevation of liver enzymes on week 4 after infection; “−” no biochemical signs of hepatitis. “Ki-67+”, positive staining on Ki-67 antigen of monthly collected liver biopsy samples or necropsy samples (more than 5% of positive nuclei); “+/−”, transient positive staining at week 4 after infection; “−”, less than 5% positively stained nuclei. “IL6/sTNFR+”, detection of IL-6 in plasma and levels of sTNFRI and RII higher than detectable levels (3.0 and 6.5 pg/ml, respectively) in bi-weekly collected plasma samples; “+/−” transient IL-6 detection and sTNFR elevation, at week 4 after infection; “−”, no IL-6, sTNFRs below detectable levels. “Viremia+”, detection of the virus in plasma; “+/−”, transient viremia in plasma samples collected at 4 weeks after infection; “−”, viremia below detectable level, 1.3 log10 PFU/ml. IgG ELISA and plaque neutralization (PRNT) titers expressed as log10 dilutions. For primary infection animals antibody titers are indicated at day of the challenge, 98 and 112 days for rhesus WE-ig7a and WE-ig7b, respectively, and 56 days for ARM-infected monkeys, ARM-iv3 and ARM-ig8. For challenged animals titers are shown at the week 10 after challenge. “SI”, stimulation index evaluated in lymphocyte proliferation assay and expressed as the mean number of radioactivity incorporated in the presence of autologous and heterologous antigens, WE/ARM (see Methods). The highest levels proliferative responses are shown in the table, 4 weeks after primary infection and 4 weeks after challenge. “CTL”, cytotoxic T lymphocyte assay (see Methods for details). Specific lysis values are shown against targets expressing NP and GP antigens, NP/GP. Although the assays were performed at effector: target ratios of 50:1, 25:1, and 12.5:1, only results from the 50:1 ratio are shown. The highest levels of CTL are shown in the table, time points after primary and challenge infection are indicated in brackets. “ND” = not done