MHC Class I Alleles Influence Set-Point Viral Load and Survival Time in Simian Immunodeficiency Virus-Infected Rhesus Monkeys

Mühl, Thorsten; Krawczak, Michael; Haaft, Peter ten; Hunsmann, Gerhard; Sauermann, Ulrike

doi:10.4049/jimmunol.169.6.3438

Cited by 146 publications

(140 citation statements)

References 44 publications

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“…An association with slow disease progression has been reported for Mamu-B*17. 25,27 In our study cohort, like in other populations, 24,27 Mamu-B*17 was linked to Mamu-B*2901 (Table 2). This composite B configuration was linked to two different A regions, one of which carried Mamu-A*02.…”

Section: Mhc Class I Haplotypessupporting

confidence: 78%

“…Mamu-B*6901 corresponds to the allele formerly termed NB2, which had been found to be associated with slow disease progression in SIV-infected monkeys of diverse origin. 25 Thus, in all animals carrying rapid progressor genotypes, slow progressor genotypes, Mamu-B*17, or configuration 30, the Mhc genotype was found to be broadly predictive of the principal disease course. Our study suggests that about 48% of the overall variation in disease progression in SIV-infected macaques can be explained by specific Mhc genotypes.…”

Section: Discussionmentioning

confidence: 90%

“…In the case of Mamu-B*01, this concurs with previous reports. 25,40 Other sequences have been reported to be expressed only at low levels, such as Mamu-B*57 and -A*1303. 24 Taken together, we have identified for the first time Mhc class I haplotypes associated with rapid disease progression.…”

Section: Discussionmentioning

confidence: 99%

“…25,29,30 Segregation analysis revealed 19 DQB1-Mhc class I haplotypes. In order to obtain Mhc class I cDNA sequences of each haplotype, we subcloned reverse transcription (RT)-PCR products from 18 animals and sequenced approximately 1600 inserts.…”

Section: Mhc Class I Haplotypesmentioning

confidence: 99%

“…Several studies have shown that single MHC antigens such as Mamu-A*01 and -B*17 are significantly associated with prolonged survival in SIV-infected rhesus macaques. 13,[25][26][27] However, monkeys sharing one or two of these MHC antigens may still exhibit a variable course of disease. 27,28 We therefore assessed the association between Mhc class I haplotypes, rather than single gene variants, and survival time in SIV-infected rhesus macaques.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Mhc class I haplotypes associated with survival time in simian immunodeficiency virus (SIV)-infected rhesus macaques

Sauermann

Siddiqui

et al. 2007

Genes Immun

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In both human immunodeficiency virus-infected humans and simian immunodeficiency virus (SIV)-infected macaques, genes encoded in the major histocompatibility complex (MHC) class I region are important determinants of disease progression. However, compared to the human human lymphocyte antigen complex, the macaque MHC region encodes many more class I genes. Macaques with the same immunodominant class I genes express additional Mhc genes with the potential to influence the disease course. We therefore assessed the association between of the Mhc class I haplotypes, rather than single gene variants, and survival time in SIV-infected rhesus macaques (Macaca mulatta). DNA sequence analysis and Mhc genotyping of 245 pedigreed monkeys identified 17 Mhc class I haplotypes that constitute 10 major genotypes. Among 81 vaccination-naive, SIV-infected macaques, 71 monkeys carried at least one Mhc class I haplotype encoding only MHC antigens that were incapable of inducing an effective anti-SIV cytotoxic T lymphocytes response. Study of these macaques enabled us to relate individual Mhc class I haplotypes to slow, medium and rapid disease progression. In a post hoc analysis, classification according to disease progression was found to explain at least 48% of the observed variation of survival time.

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Section: Mhc Class I Haplotypessupporting

confidence: 78%

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Mhc Class I Haplotypesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Mhc class I haplotypes associated with survival time in simian immunodeficiency virus (SIV)-infected rhesus macaques

Sauermann

Siddiqui

et al. 2007

Genes Immun

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Nonhuman Primate Models for HIV/AIDS Vaccine Development

et al. 2013

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The development of HIV vaccines has been hampered by the lack of an animal model that can accurately predict vaccine efficacy. Chimpanzees can be infected with HIV-1 but are not practical for research. However, several species of macaques are susceptible to the Simian Immunodeficiency Viruses (SIV) that causes a disease in macaques that closely mimics HIV in humans. Thus, macaque-SIV models of HIV infection have become a critical foundation for AIDS vaccine development. Here, we examine the multiple variables and considerations that must be taken into account to use this NHP model effectively. These include the species and subspecies of macaques, virus strain, dose and route of administration and macaque genetics including Major Histocompatibility Complex molecules that affect immune responses and other virus restriction factors. We illustrate how these NHP models can be used to carry out studies of immune responses in mucosal and other tissues than could not easily be performed on human volunteers. Futhermore macaques are an ideal model system to optimize adjuvants, test vaccine platforms, and identify correlates of protection that can advance the HIV vaccine field. We also illustrate techniques used to identify different macaque lymphocyte populations and review some poxvirus vaccine candidates that are in various stages of clinical trials. Understanding how to effectively use this valuable model will greatly increase the likelihood of finding a successful vaccine for HIV.

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Genetic characterization of rhesus macaques (Macaca mulatta) in Nepal

Kyes

Jones‐Engel

Chalise

et al. 2006

American J Primatol

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Indian-origin rhesus macaques (Macaca mulatta) have long served as an animal model for the study of human disease and behavior. Given the current shortage of Indian-origin rhesus, many researchers have turned to rhesus macaques from China as a substitute. However, a number of studies have identified marked genetic differences between the Chinese and Indian animals. We investigated the genetic characteristics of a third rhesus population, the rhesus macaques of Nepal. Twenty-one rhesus macaques at the Swoyambhu Temple in Kathmandu, Nepal, were compared with more than 300 Indian- and Chinese-origin rhesus macaques. The sequence analyses of two mitochondrial DNA (mtDNA) loci, from the HVS I and 12 S rRNA regions, showed that the Nepali animals were more similar to Indian-origin than to Chinese-origin animals. The distribution of alleles at 24 short tandem repeat (STR) loci distributed across 17 chromosomes also showed greater similarity between the Nepali and Indian-origin animals. Finally, an analysis of seven major histocompatibility complex (MHC) alleles showed that the Nepali animals expressed Class I alleles that are common to Indian-origin animals, including Mamu-A*01. All of these analyses also revealed a low level of genetic diversity within this Nepali rhesus sample. We conclude that the rhesus macaques of Nepal more closely resemble rhesus macaques of Indian origin than those of Chinese origin. As such, the Nepali rhesus may offer an additional resource option for researchers who wish to maintain research protocols with animals that possess key genetic features characteristic of Indian-origin rhesus macaques.

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MHC Class I Alleles Influence Set-Point Viral Load and Survival Time in Simian Immunodeficiency Virus-Infected Rhesus Monkeys

Cited by 146 publications

References 44 publications

Mhc class I haplotypes associated with survival time in simian immunodeficiency virus (SIV)-infected rhesus macaques

Mhc class I haplotypes associated with survival time in simian immunodeficiency virus (SIV)-infected rhesus macaques

Nonhuman Primate Models for HIV/AIDS Vaccine Development

Genetic characterization of rhesus macaques (Macaca mulatta) in Nepal

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