Experimental Infection of Chimpanzees with Dengue Viruses

Abstract

Single strains of dengue (DEN) virus types 1–4 at low passage levels after isolation in Thailand, New Caledonia or the Philippine Islands produced no overt, febrile or hematologically detectable subclinical disease in chimpanzees inoculated subcutaneously and intradermally. After primary inoculation, viremias occurred usually from days 2 or 3 through days 5–7. Virus was detected in serum with about equal frequencies by either mosquito inoculation or LLCMK2 monkey kidney cell cultural technics, although mosquito inoculations usually yielded higher titers of virus. After secondary challenge with DEN 2 virus 26 mo after primary infection with DEN 1, 2, 3 or 4, viremias lasting 2–4 days occurred during days 3–6 in one or two chimpanzees originally infected with DEN 1 or DEN 4, but not with DEN 2 or DEN 3. Primary homologous DEN hemagglutination-inhibition (HI) antibody responses were greater than heterologous in pairs of young chimpanzees born in the U.S.A. and inoculated with DEN 3 or DEN 4. However, primary homologous DEN HI antibody responses were similar to heterologous responses in five adult chimpanzees from Africa inoculated with DEN 1, 2, 3 or 4 viruses and in three young chimpanzees born in the U.S.A. and inoculated with DEN 2 virus. Homologous and heterologous neutralizing (N) antibodies were found in serum 4–6 wk after primary infection of adult chimpanzees, but only homologous DEN 2 N antibodies were detected in three young chimpanzees. Preexisting antibodies to other flaviviruses were found in sera of some chimpanzees from Africa, and broad flavivirus anamnestic HI antibody responses occurred after primary inoculations of DEN viruses. Broad flavivirus HI antibody responses were also observed after primary DEN inoculations in three young chimpanzees born and housed near New York City and without preexisting flavivirus antibodies. Following secondary challenge with DEN 2 virus, HI and complement fixation antibody responses occurred to all DEN types and to related flaviviruses.