The concentration of human immunodeficiency virus type 1 (HIV-1) particles in blood plasma is very predictive of the subsequent disease course in an infected individual; its measurement has become one of the most important parameters for monitoring clinical status. Steady-state virus levels in plasma reflect a balance between the rates of virions entering and leaving the peripheral blood. We analyzed the rate of virus clearance in the general circulation in rhesus macaques receiving a continuous infusion of cell-free particles in the presence and absence of virus-specific antibodies. Here we show, by measuring virion RNA, particle-associated p24 Gag protein and virus infectivity, that the clearance of physical and infectious particles from a primary, dual-tropic virus isolate, HIV-1DH12, is very rapid in naive animals, with half-lives ranging from 13 to 26 minutes. In the presence of high-titer HIV-1DH12-specific neutralizing antibodies, the half-life of virion RNA was considerably reduced (to 3.9-7.2 minutes), and infectious virus in the blood became undetectable. Although physical virus particles were eliminated extravascularly, the loss of virus infectivity in the blood reflected the combined effects of extravascular clearance and intravascular inactivation of HIV-1 infectivity due to antibody binding.

Hamsters infected with Treponema pallidum Nichols (venereal syphilis), T. pallidum Bosnia A (endemic syphilis), or T. pertenue (frambesia, or yaws) developed substantial resistance to homologous reinfection. Hamsters infected for 10 weeks developed no lesions, and their lymph nodes contained fewer treponemes after reinfection with the same strain. The degree of cross-resistance among the treponemes correlated well with pathological changes occurring in infected hamsters and with the persistence of treponemal antigen during primary infection. Only hamsters infected with T. pallidum Bosnia A developed substantial resistance to heterologous reinfection. These animals also had extensive chronic skin lesions and lymph nodes containing measurable numbers of treponemes. Frambesial hamsters had less extensive lesions and were resistant to T. pallidum Nichols and, to a lesser extent, to T. pallidum Bosnia A. Hamsters infected with T. pallidum Nichols developed no cutaneous lesions and were resistant only to reinfection with T. pertenue. Confirmation of these results was obtained in normal hamsters infused with syphilitic (Nichols or Bosnia A) or frambesial immune cells and challenged with homologous or heterologous treponemes. The causative agents of syphilis and frambesia (yaws) have not been distinguished by morphological (24, 26) or immunological (8) criteria. Some investigators (7) believe that the treponemes are identical and that differences in clinical manifestations result from varying host responses, perhaps mediated in part by climactic conditions. Others (2-4) propose that although the virulent treponemes evolved from a common precursor, they now are in fact different. Conflicting results have also been reported on cross-resistance to the virulent treponemes. Human patients with frambesia are protected against syphilis (5, 19, 21, 22), and rabbits infected with frambesia or syphilis show some resistance to challenge with heterologous virulent treponemes (10, 24, 25). There is also evidence (23) that infection of rabbits with Treponema pallidum Nichols (venereal syphilis) induces

Passive transfer of frambesial immune serum is capable of conferring complete protection on hamsters against challenge with Treponema pallidum ssp. pertenue. Treponemicidal activity in the pooled immune serum is relatively high. Immune serum and its immunoglobulin fractions, especially IgG2, also killed T. pallidum ssp. pertenue in vitro. Treponemicidal activity was present only when immune serum was administered to hamsters within a short time (three days) of frambesial challenge. By contrast, administration of pooled immune serum to hamsters infected for more than one week failed to reduce the number and size of lesions and the weight and number of treponemes in the lymph nodes. These results suggest that hamsters can develop the humoral components necessary to protect them against frambesial challenge, but these components are unable to destroy treponemes at the primary foci of infection.