Inhibition of adaptive immune responses leads to a fatal clinical outcome in SIV-infected pigtailed macaques but not vervet African green monkeys

Autor: Vanessa M. Hirsch, Ming‐ming Li, Russell Byrum, Simoy Goldstein, Roland Zahn, Amitinder Kaur, Melisa D. Rett, Sarah Pryputniewicz, David C. Montefiori, Charles R. Brown, Jonathan S. Allan, Jörn E. Schmitz, Haili Tang
Jazyk: angličtina
Rok vydání: 2009
Předmět:
animal diseases
Simian Acquired Immunodeficiency Syndrome
Adaptive Immunity
CD8-Positive T-Lymphocytes
medicine.disease_cause
0302 clinical medicine
Chlorocebus aethiops
lcsh:QH301-705.5
In Situ Hybridization
0303 health sciences
Reverse Transcriptase Polymerase Chain Reaction
virus diseases
Acquired immune system
Immunohistochemistry
3. Good health
Virology/Immunodeficiency Viruses
Virology/Animal Models of Infection
Simian Immunodeficiency Virus
Macaca nemestrina
Antibody
Research Article
lcsh:Immunologic diseases. Allergy
endocrine system
Blotting
Western
Immunology
B-Lymphocyte Subsets
Viremia
Biology
Microbiology
Lymphocyte Depletion
Virus
Immunophenotyping
03 medical and health sciences
Immune system
Immunology/Immunity to Infections
Virology
Genetics
medicine
Animals
Molecular Biology
030304 developmental biology
Simian immunodeficiency virus
Antigens
CD20
medicine.disease
Chronic infection
Viral replication
lcsh:Biology (General)
biology.protein
Parasitology
lcsh:RC581-607
030215 immunology
Zdroj: PLoS Pathogens, Vol 5, Iss 12, p e1000691 (2009)
PLoS Pathogens
ISSN: 1553-7374
1553-7366
Popis: African green monkeys (AGM) and other natural hosts for simian immunodeficiency virus (SIV) do not develop an AIDS-like disease following SIV infection. To evaluate differences in the role of SIV-specific adaptive immune responses between natural and nonnatural hosts, we used SIVagmVer90 to infect vervet AGM and pigtailed macaques (PTM). This infection results in robust viral replication in both vervet AGM and pigtailed macaques (PTM) but only induces AIDS in the latter species. We delayed the development of adaptive immune responses through combined administration of anti-CD8 and anti-CD20 lymphocyte-depleting antibodies during primary infection of PTM (n = 4) and AGM (n = 4), and compared these animals to historical controls infected with the same virus. Lymphocyte depletion resulted in a 1-log increase in primary viremia and a 4-log increase in post-acute viremia in PTM. Three of the four PTM had to be euthanized within 6 weeks of inoculation due to massive CMV reactivation and disease. In contrast, all four lymphocyte-depleted AGM remained healthy. The lymphocyte-depleted AGM showed only a trend toward a prolongation in peak viremia but the groups were indistinguishable during chronic infection. These data show that adaptive immune responses are critical for controlling disease progression in pathogenic SIV infection in PTM. However, the maintenance of a disease-free course of SIV infection in AGM likely depends on a number of mechanisms including non-adaptive immune mechanisms.
Author Summary Simian immunodeficiency virus (SIV) is a naturally occurring infection in a wide range of African nonhuman primates, including African green monkeys (AGM), which generally results in a clinically inapparent infection. In contrast, SIV infection of Asian nonhuman primates such as macaques can result in an AIDS-like disease similar to that observed in humans infected with human immunodeficiency virus (HIV). This different pathogenic outcome occurs despite similar levels of viremia. In order to evaluate the contribution of adaptive immune responses to these different outcomes, we transiently inhibited the generation of CD8+ and CD20+ lymphocyte-mediated immune responses in vervet AGM and pigtailed macaques (PTM) during primary SIV infection. PTM experienced higher viremia and accelerated progression to disease, whereas AGM showed only a short prolongation of peak viremia but exhibited no signs of illness. These results demonstrate that protection against development of disease in AGM does not solely rely on adaptive immune responses. Future efforts should aim to determine the underlying mechanisms that enable natural hosts to cope with SIV infection and to apply these findings to develop new treatment modalities for humans infected with HIV.
Databáze: OpenAIRE
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