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Abstract
INFLUENCE OF ITAM MOTIF OF CHIMERIC SIMIAN/HUMAN IMMUNODEFICENCY VIRUS SHIVSBG-NEFYE ON VIRULENCE IN CHINESE RHESUS MACAQUES
LAFONT B, GLOECKLER L, BEYER C, EINIUS S, GUT J, AUBERTIN A
The SHIVsbg, expressing the Vpu, Tat, Rev and Env proteins of HIV1 Lai was shown to be pathogenic for rhesus macaques and cynomolgus monkeys.To study factors susceptible to modulate the virulence of the virus, we mutated the amino acids 17-18 RQ in YE. These changes conferred to SHIVsbg the ability to replicate in unstimulated macaque PBMC.
Juvenile macaques inoculated intravenously or orally with SHIVsbg-nefYE developed persistent infection. one week post-infection, the cellular viral load was 10 to 50 times lower in orally infected monkeys than in i.v. inoculated group. Afterwards the cellular viremia was similar for the two groups with 50-250 infected PBMC per million cells. A lymphadenopathy was observed during the first weeks of infection. The hematological data showed a general decrease of lymphocyte population in four out of five animals with a loss of 35-40% of CD4 in three of them. All macaques lost weight during the first 17 weeks. Of note, the cellular viral load during the first weeks of infection was about 125 times lower than the value measured during the infection by the SHIVsbg and modifications of the hematologic parameters were also less pronounced although the intravenous virus doses were similar (440 TCID50).
Viruses isolated two years post-inoculation did conserve the same coreceptor usage as the inoculated virus but had lost the ability to replicate in unstimulated macaque PBMC. Different alterations in the nef gene ITAM motif were responsible for this phenotype.
These data demonstrate that the ITAM domain is inactivated in animals developing an acute antiviral immune response and may be detrimental to viral replication, perhaps by interfering with other well-conserved function of SIV nef protein.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
86
Suggested Citation
"LAFONTB, et al.
INFLUENCE OF ITAM MOTIF OF CHIMERIC SIMIAN/HUMAN IMMUNODEFICENCY VIRUS SHIVSBG-NEFYE ON VIRULENCE IN CHINESE RHESUS MACAQUES.
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
86"
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