Natural Scrub Typhus Antibody Suppresses HIV CXCR4(X4) Viruses.

[scrub typhus]

Viral load generally rises in HIV-infected individuals with a concomitant infection , but falls markedly in some individuals with scrub typhus (ST ), a common Asian rickettsial infection . ST infection appears to shift the viral population from CXCR 4 -using (X 4 ) to CCR 5 -utilizing (R 5 ) strains , and there is evidence of cross-reactivity between ST-specific antibodies and HIV-1 . We examined the mechanism of ST suppression of HIV by measuring the effects of ST infection on X 4 and R 5 viruses in vivo and in vitro , and assessing the relative contributions of antibodies and chemokines to the inhibitory effect . In vivo , a single scrub typhus plasma infusion markedly reduced the subpopulation of HIV-1 viruses using the X 4 co -receptor in all 8 recipients , and eliminated X 4 viruses 6 patients . In vitro , the 14 ST sera tested all inhibited the replication of an X 4 but not an R 5 virus . This inhibitory effect was maintained if ST sera were depleted of chemokines but was lost upon removal of antibodies . Sera from STinfected mice recognized a target that co -localized with X 4 HIV gp 120 in immunofluorescent experiments . These in vivo and in vitro data suggest that acute ST infection generates cross-reactive antibodies that produce potent suppression of CXCR 4 - but not CCR 5 -using HIV-1 viruses . ST suppression of HIV replication could reveal novel mechanisms that could be exploited for vaccination strategies , as well as aid in the development of fusion inhibitors and other new therapeutic regimens . This also appears to be the first instance where one pathogen is neutralized by antibody produced in response to infection by a completely unrelated organism .