SERUM NEUTRALIZATION OF FELINE IMMUNODEFICIENCY VIRUS IS MARKEDLY DEPENDENT ON PASSAGE HISTORY OF THE VIRUS AND HOST SYSTEM

Sera from feline immunodeficiency virus (FIV)-infected cats exhibited extremely low levels of neutralizing antibodies against virus passaged a few times in vitro (low passage), when residual infectivity was ass ayed in the CD3(+) CD4(-) CD8(-) MBM lymphoid cell line or mitogen-act ivated peripheral blood mononuclear cells. By sharp contrast, elevated titers of highly efficient neutralizing activity against FIV were mea sured, by use of high-passage virus, in assays on either the fibroblas toid Cr FK or MBM cell line. However, high-passage virus behaved the s ame as low-passage virus after one in vivo passage in a specific-patho gen-free cat and reisolation. Subneutralizing concentrations of infect ed cat sera enhanced the production of low-passage virus by MBM cells, an effect not seen with high-passage virus in CrFK cells. These quali tative and quantitative discrepancies could not be attributed to diffe rences in the amount of immunoreactive viral material, to the amount o f infectious virus present in the viral stocks, or to the presence of anti cell antibodies. The observed effects were most likely due to the different passage history of the viral preparations used. The observa tion that neutralizing antibodies detected with high-passage virus wer e broadly cross-reactive in assays with CrFK Cells but isolate specifi c in MBM cells suggests also that the cell substrate can influence the result of FIV neutralization assays. This possibility could not be te sted directly because FIV adapted to grow in CrFK cells had little inf ectivity for lymphoid cells and vice versa. In vitro exposure to infec ted cat sera had little or no effect on the ability of in vivo-passage d FIV to infect cats. These data reveal no obvious relationship betwee n titers against high-passage virus and ability to block infectivity o f FIV in cats and suggest caution in the use of such assays to measure vaccine efficacy. In conclusion, by contrast with what has been previ ously reported for the use of CrFK cells and high-passage virus, both natural and experimental infections of cats with FIV generate poor neu tralizing antibody responses with regard to in vivo protection.