Steve Norley

Simian immunodeficiency virus from African green monkeys.

When virologists talk about African green monkeys (AGM), they usually mean species belonging to the subgenus Cercopithecus aethiops of the genus Cercopithecus. This genus can be subdivided into eight subgenera (C. mona, C. cephus, C. mitis, C. i’hoesti, C. hamlyni, C. neglectus, C. diana, C. aethiops). A subgenus comprises several species and is defined by the common ecological specialization (“life-style”) of its member species. Therefore, species belonging to the same subgenus are geographically separated, as they would otherwise compete for resources. Some of the species can be further subdivided into altogether over 70 subspecies (for the entire genus) distinguished by subtle morphological differences. Members of similar subspecies usually do not mate in the wild. There are a number of excellent books delineating monkey species (GRZIMEK 1988; HILL 1972; NAPIER and NAPIER 1985).

Two Distinct Gamma-2 Herpesviruses in African Green Monkeys: a Second Gamma-2 Herpesvirus Lineage among Old World Primates?

ABSTRACT Primate gamma-2 herpesviruses (rhadinoviruses) have so far been found in humans (Kaposis sarcoma-associated herpesvirus [KSHV], also called human herpesvirus 8), macaques (Macaca spp.) (rhesus rhadinovirus [RRV] and retroperitoneal fibromatosis herpesvirus [RFHV]), squirrel monkeys (Saimiri sciureus) (herpesvirus saimiri), and spider monkeys (Ateles spp.) (herpesvirus ateles). Using serological screening and degenerate consensus primer PCR for the viral DNA polymerase gene, we have detected sequences from two distinct gamma-2 herpesviruses, termedChlorocebus rhadinovirus 1 (ChRV1) and ChRV2, in African green monkeys. ChRV1 is more closely related to KSHV and RFHV, whereas ChRV2 is closest to RRV. Our findings suggest the existence of two distinct rhadinovirus lineages, represented by the KSHV/RFHV/ChRV1 group and the RRV/ChRV2 group, respectively, in at least two Old World monkey species. Antibodies to members of the RRV/ChRV2 lineage may cross-react in an immunofluorescence assay for early and late KSHV antigens.

Protection of rhesus macaques from SIV infection by immunization with different experimental SIV vaccines.

The immunogenicity and efficacy of an inactivated whole SIVmac (32H) preparation adjuvanted with muramyl dipeptide (SIV-MDP) and a gp120-enriched SIVmac (32H) ISCOM preparation (SIV-ISCOM), were compared by immunizing four rhesus macaques (Macaca mulatta) four times with SIV-MDP and four others in the same way with SIV-ISCOM. Two monkeys immunized with whole inactivated measles virus (MV) adjuvanted with MDP (MV-MDP) and two monkeys immunized with MV-ISCOM served as controls. In the SIV-ISCOM-immunized monkeys higher SIV-specific serum antibody titres were found than in the SIV-MDP-immunized monkeys. In contrast to the MV-immunized monkeys all SIV-MDP- and SIV-ISCOM-immunized monkeys were protected against intravenous challenge 2 weeks after the last immunization with 10 median monkey infectious doses (MID50) of a cell-free SIVmac (32H) challenge stock propagated in the human T-cell line C8166. After 43 weeks the protected monkeys were reboosted and 2 weeks later rechallenged with 10 MID50 of the same virus produced in peripheral blood mononuclear cells (PBMC) from a rhesus macaque. None of these animals proved to be protected against this challenge. In a parallel experiment in which the same numbers of monkeys were immunized in the same way, the animals were challenged intravenously with 10 MID50 of PBMC from an SIVmac (32H)-infected rhesus macaque. Two out of four SIV-MDP- and two out of four SIV-ISCOM-immunized monkeys proved to be protected from SIV infection.

Induction of antibodies against SIV antigens after intramuscular nucleic acid inoculation using complex expression constructs

By studying the infection of rhesus macaques with simian immunodeficiency virus (SIVmac) the potential of nucleic acid immunisation against AIDS can be evaluated. As a first step towards the development of suitable expression constructs, the levels and the durations of expression elicited by the house-keeping gene promoters of the murine phospho-glycerate kinase (PGK) gene and rat proto-ras 1Ha, a lentiviral LTR and the CMV-intron A promoter were tested in BALB/c mice intramuscularly inoculated with marker gene constructs encoding luciferase. The expression levels achieved by the CMV-intron A and the lentiviral promoter were comparably high, and also the PGK promoter induced a high level of expression for at least 64 days. Following the inoculation of plasmids comprising single or multiple genes of SIV, the induction of specific antibodies directed against SIV antigens was demonstrated. We previously showed in vitro that int- and nef-defective mutants of SIVmac were able to initiate a limited and self-abortive infection of permissive cells in the absence of chromosomal integration of the viral DNA. Intramuscular inoculations in monkeys using int-defective proviral DNA of SIV will show whether an increased immune response may be induced by expression of viruses undergoing a self-limited replication in vivo.

Chemoattractant Factors and the Control of Human Immunodeficiency Virus Replication

Factors secreted by CD8(+) T cells have been described to suppress immunodeficiency virus replication. The research efforts to identify these factors led to the proposal of some candidate proteins as being responsible for the antiviral effects. Chemokines and IL-16 are secreted by CD8(+) T cells and inhibit HIV replication through different mechanisms. However, their antiviral properties cannot fully explain the inhibitory activities found in cell culture supernatants from CD8(+) T cells.

HIV: Virologie und Impfungen

Die kausale Therapie viraler Erkrankungen ist trotz unbestreitbarer Erfolge in einigen Teilbereichen nach wie vor sehr schwierig. Dagegen last sich an zahlreichen Beispielen zeigen, das die Einfuhrung von Schutzimpfungen zu einem drastischen Ruckgang virusbedingter Epidemien gefuhrt und im Falle der Pocken sogar die Ausrottung des Erregers ermoglicht hat. Es uberrascht daher nicht, das schon sehr bald nach der eindeutigen Identifizierung eines Retrovirus als Ursache der erworbenen Immunschwache AIDS zahlreiche Gruppen mit der Entwicklung eines Impfstoffes begonnen haben. In den vergangenen zwolf Monaten konnte daher eine Reihe von potentiellen Vakzinen in Schimpansen getestet werden. Das enttauschende Ergebnis all dieser Versuche ist aber, das keines der geimpften Tiere gegen eine Infektion mit dem AIDS-Erreger HIV (Humanes Immundefizienz-Virus) geschutzt war. Die moglichen Ursachen fur diese Miserfolge und die moglichen Auswege aus diesem Dilemma werden in den folgenden Ausfuhrungen diskutiert.