Jan Münch

Co-receptor Usage of BOB/GPR15 in Addition to CCR5 Has No Significant Effect on Replication of Simian Immunodeficiency Virus In Vivo

Human immunodeficiency virus type 2 (HIV-2) and the closely related simian immunodeficiency viruses (SIVs) frequently use the orphan receptor BOB/GPR15 in addition to the chemokine receptor CCR5 for efficient entry and replication. However, the role of BOB/GPR15 in replication and pathogenesis of HIV-2 and SIV in vivo is unclear. This study shows that a single amino acid substitution in the V3 loop of the pathogenic SIVmac239 clone, 321P-->S, impaired the ability to use BOB/GPR15 for entry and replication but had little effect on the ability to use CCR5. This envelope variant replicated with an efficiency comparable with the parental SIVmac239 isolate in rhesus macaques. Furthermore, the mutant genotype and phenotype remained stable even after the onset of immunodeficiency. These results suggest that this cofactor plays only a minor role for the pathogenicity of the HIV-2/SIVmac/SIVsm group of primate lentiviruses.

Natural SIV Infection

Publisher Summary nThis chapter aims to provide a brief overview of the distribution and biological properties of primate lentiviruses and emergence of the human immunodeficiency viruses (HIV). The discovery that HIV and acquired immune deficiency syndrome (AIDS) are the result of relatively recent zoonotic transmissions of simian immunodeficiency virus (SIVs) from African nonhuman primates (NHPs) to humans, aroused a great deal of interest in natural primate lentiviral infections. Effective noninvasive methodologies for the detection and analysis of SIV-specific antibodies and virion RNA in fecal and urine samples of wild NHPs have been developed. These methods have allowed large-scale seroepidemiological and molecular studies of wild primate populations and yielded key insights into the genetic diversity and natural history of primate lentiviruses. SIVs or SIV-specific antibodies have been detected in more than 40 different African NHPs. HIV and SIV belong to the genus of lentiviruses and are generally referred to as “immunodeficiency” viruses.Publisher Summary This chapter aims to provide a brief overview of the distribution and biological properties of primate lentiviruses and emergence of the human immunodeficiency viruses (HIV). The discovery that HIV and acquired immune deficiency syndrome (AIDS) are the result of relatively recent zoonotic transmissions of simian immunodeficiency virus (SIVs) from African nonhuman primates (NHPs) to humans, aroused a great deal of interest in natural primate lentiviral infections. Effective noninvasive methodologies for the detection and analysis of SIV-specific antibodies and virion RNA in fecal and urine samples of wild NHPs have been developed. These methods have allowed large-scale seroepidemiological and molecular studies of wild primate populations and yielded key insights into the genetic diversity and natural history of primate lentiviruses. SIVs or SIV-specific antibodies have been detected in more than 40 different African NHPs. HIV and SIV belong to the genus of lentiviruses and are generally referred to as “immunodeficiency” viruses.

VIRIP: Ein natürlicher HIV-Hemmstoff mit einem neuartigen Wirkmechanismus

Es ist seit langem bekannt, dass eine Reihe von korpereigenen Verbindungen die Vermehrung von HIV — zumindest teilweise — unterdrucken kann. Beispielsweise fuhrte die Entdeckung, dass Chemokine die Korezeptoren von HIV binden und dadurch die virale Infektion verhindern, zur Entwicklung einer ganzen Reihe von neuen Inhibitoren, die verschiedene Schritte des Eintritts von HIV in die Wirtszelle blockieren (Moore u. Stevenson 2000; Ray u. Doms 2006). Haufig erwies es sich allerdings als schwierig, antivirale Verbindungen in menschlichen Geweben und Korperflussigkeiten aufzureinigen und zu charakterisieren. So ist auch 20 Jahre nach der Erstbeschreibung unklar, welcher antivirale Faktor von CD8+-T Zellen sekretiert wird (Walker et al. 1986), obwohl bei der Suche danach zahlreiche andere antivirale Verbindungen entdeckt wurden (Levy 2003). Wesentliche Hindernisse bei der Charakterisierung korpereigener antiviraler Substanzen sind die sehr begrenzten Mengen an menschlichem Untersuchungsmaterial und das Fehlen von standardisierten Methoden zur Aufreinigung der Inhibitoren.