A Species-Specific Amino Acid Difference in the Macaque CD4 Receptor Restricts Replication by Global Circulating HIV-1 Variants Representing Viruses from Recent Infection
| العنوان: | A Species-Specific Amino Acid Difference in the Macaque CD4 Receptor Restricts Replication by Global Circulating HIV-1 Variants Representing Viruses from Recent Infection |
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| المؤلفون: | Julie Overbaugh, Sandra Emery, Elizabeth Laws, Daryl Humes |
| المصدر: | Journal of Virology. 86:12472-12483 |
| بيانات النشر: | American Society for Microbiology, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Green Fluorescent Proteins, Immunology, HIV Infections, Virus Replication, medicine.disease_cause, Microbiology, Macaque, Virus, Cell Line, Evolution, Molecular, Species Specificity, Virology, biology.animal, medicine, Animals, Humans, Receptor, DNA Primers, Genetics, Infectivity, biology, env Gene Products, Human Immunodeficiency Virus, Genetic Variation, Simian immunodeficiency virus, Macaca mulatta, Genome Replication and Regulation of Viral Gene Expression, Disease Models, Animal, Amino Acid Substitution, Viral replication, Cell culture, Viral Receptor, Insect Science, CD4 Antigens, Host-Pathogen Interactions, HIV-1, Mutagenesis, Site-Directed, Simian Immunodeficiency Virus |
| الوصف: | HIV-1 replicates poorly in macaque cells, and this had hindered the advancement of relevant nonhuman primate model systems for HIV-1 infection and pathogenesis. Several host restriction factors have been identified that contribute to this species-specific restriction to HIV-1 replication, but these do not fully explain the poor replication of most strains of HIV-1 in macaque cells. Only select HIV-1 envelope variants, typically those derived from viruses that have been adapted in cell culture, result in infectious chimeric SIVs encoding HIV-1 envelope (SHIVs). Here we demonstrate that most circulating HIV-1 variants obtained directly from infected individuals soon after virus acquisition do not efficiently mediate entry using the macaque CD4 receptor. The infectivity of these viruses is ca. 20- to 50-fold lower with the rhesus and pig-tailed macaque versus the human CD4 receptor. In contrast, culture-derived HIV-1 envelope variants that facilitate efficient replication in macaques showed similar infectivity with macaque and human CD4 receptors (within ∼2-fold). The ability of an envelope to mediate entry using macaque CD4 correlated with its ability to mediate entry of cells expressing low levels of the human CD4 receptor and with soluble CD4 sensitivity. Species-specific differences in the functional capacity of the CD4 receptor to mediate entry mapped to a single amino acid difference at position 39 that is under strong positive selection, suggesting that the evolution of CD4 may have been influenced by its function as a viral receptor. These results also suggest that N39 in human CD4 may be a critical residue for interaction of transmitted HIV-1 variants. These studies provide important insights into virus-host cell interactions that have hindered the development of relevant nonhuman primate models for HIV-1 infection and provide possible markers, such as sCD4 sensitivity, to identify potential HIV-1 variants that could be exploited for development of better SHIV/macaque model systems. |
| تدمد: | 1098-5514 0022-538X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::60fa0923e7d5968b03681dd803f2a7db https://doi.org/10.1128/jvi.02176-12 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....60fa0923e7d5968b03681dd803f2a7db |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10985514 0022538X |
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