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HIV-1 infection in pigtailed macaques
1Henry M. Jackson Foundation Research Laboratory, Rockville, Maryland 20850.
Abstract:
Four pigtailed macaques were inoculated with autologous cells expressing low levels of human immunodeficiency virus type 1 (HIV-1). During the first 10 weeks, infectious virus was recovered from peripheral blood mononuclear cells (PBMCs) and lymph nodes from three of the animals. Subsequently, HIV-1 DNA was frequently detected in uncultured PBMCs from all three animals, and virus was isolated from one of them at weeks 38 and 61. The fourth animal, which was rechallenged at week 10 with cell-free virus isolated from one of the others, never became virus isolation positive, but harbored HIV-1 proviral genomes. These virus infections were accompanied by the development of varied HIV-1-specific humoral immune responses. Antibodies to gp160 were first apparent at week 8 in the three initially infected animals and persisted. The animal from whom virus was isolated at late times also developed persisting antibodies to HIV-1 p24 and gp120. Antibodies to gp120 and gp160 became apparent in the rechallenged animal at 1 week following reinoculation, but they waned with time. In vivo passage of the virus was attempted at week 6. One recipient pigtailed macaque and one recipient cynomolgus monkey failed to become detectably infected following transfusion of virus-positive blood and lymph node cells. The long-term presence of HIV-1-specific antibodies and proviral genomes in these animals, and the recovery of infectious virus more than 1 year following inoculation, are indicative of persistent infection, and confirm previous reports that pigtailed macaques are susceptible to HIV-1.
Insights
Pigtailed macaques inoculated with human immunodeficiency virus type 1 (HIV-1) showed persistent infection, with infectious virus recovered over a year later. This confirms macaque susceptibility to HIV-1 and demonstrates varied immune responses.
Area of Science:
- Virology
- Immunology
- Primate Models
Background:
- The pigtailed macaque is a potential model for studying human immunodeficiency virus type 1 (HIV-1) infection.
- Understanding persistent HIV-1 infection and immune responses in vivo is crucial for developing effective therapies and vaccines.
Purpose of the Study:
- To investigate the susceptibility of pigtailed macaques to HIV-1 infection.
- To characterize the viral dynamics and host immune responses following experimental HIV-1 inoculation.
Main Methods:
- Four pigtailed macaques were inoculated with autologous cells expressing low levels of HIV-1.
- Infectious virus recovery, HIV-1 DNA detection in PBMCs, and antibody responses (gp160, p24, gp120) were monitored over time.
- In vivo passage attempts were made using blood and lymph node cells from infected animals.
Main Results:
- Three of four macaques showed infectious virus recovery from PBMCs and lymph nodes within 10 weeks.
- Persistent HIV-1 DNA was detected in PBMCs, with infectious virus isolated up to week 61 in one animal.
- Varied HIV-1-specific humoral immune responses, including antibodies to gp160, p24, and gp120, were observed.
Conclusions:
- Pigtailed macaques are susceptible to persistent HIV-1 infection, with viral shedding and proviral DNA detectable for over a year.
- The study confirms the utility of pigtailed macaques as a model for HIV-1 research.
- Observed immune responses provide insights into the host-pathogen interactions during chronic HIV-1 infection in this primate model.