Dose-dependent viremia and the differential immunoglobulin response of hamsters to Powassan virus

Hamsters injected subcutaneously with a single "low-dose" inoculum (10 mouse LD 50 ) of Powassan virus developed viremia titering 10 6.2 mouse LD 50 per milliliter of blood whereas hamsters receiving a "high-dose" inoculum of 10 5.0 mouse LD 50 of virus developed a viremia of only 10 4.5 mouse LD 50 per milliliter.Hemagglutination-inhibiting (HI) antibodies were first detected 7 days following the "low-dose" inoculation and attained maximum titers of 160. The HI antibody response to the "high-dose" virus inoculation began on the 5th day, at a time when viremia was present, and antibody titers did not exceed 40. Sucrose-density analysis and 2-mercaptoethanol treatment of sera revealed that IgM antibodies were induced by both inocula but animals receiving a low dose of virus produced higher IgG responses than did animals receiving a high dose of virus. Neutralizing antibodies, which did not appear until 30 days post inoculation, were present at a log neutralizing index (NI) of 2.0 at 60 days in animals receiving 10 mouse LD 50 of virus and at a log NI of 1.0 in those receiving 10 5.0 mouse LD 50 . The NI of IgG was equal to the index for total gamma globulin in samples that contained both IgM and IgG as demonstrated by the HI test.Animals originally exposed to a "low-dose" inoculum produced a more prolonged anamnestic response when challenged 63 days later with 10 5.0 mouse LD 50 of virus than did animals receiving a second inoculum containing only 10 3.0 or 10 mouse LD 50 of virus. In contrast, poor secondary antibody responses were elicited by challenge doses of 10 5.0 , 10 3.0 , or 10 mouse LD 50 of virus in animals that originally had received a "high-dose" of virus. IgM and IgG classes of antibody were induced in all secondary responses and the log NI of each group of animals was elevated by about 1 during anamnesis.