Journal
JOURNAL OF VIROLOGY
Volume 74, Issue 13, Pages 5836-5844Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.74.13.5836-5844.2000
Keywords
-
Categories
Funding
- NCRR NIH HHS [RR-00169, P51 RR000169] Funding Source: Medline
- PHS HHS [R01-A139415] Funding Source: Medline
Ask authors/readers for more resources
The human and simian immunodeficiency virus (HN-I and SIVmac) transmembrane proteins contain unusually long intracytoplasmic domains (ICD-TM). These domains are suggested to play a role in envelope fusogenicity, interaction with the viral matrix protein during assembly, viral infectivity, binding of intracellular calmodulin, disruption of membranes, and induction of apoptosis, Here we describe a novel mutant virus, SIVmac-M4, containing multiple mutations in the coding region for the ICD-TM of pathogenic molecular clone STVmac239, Parental Sn7mac239-Nef+ produces high-level persistent viremia and simian AIDS in both juvenile and newborn rhesus macaques, The ICD-TM region of SIVmac-M4 contains three stop codons, a +1 frameshift, and mutation of three highly conserved, charged residues in the conserved C-terminal alpha-helix referred to as lentivirus lytic peptide 1 (LLP-1). Overlapping reading frames for tat, rev, and nef are not affected by these changes. In this study, four juvenile macaques received SIVmac-M4 by intravenous injection. plasma viremia, as measured by branched-DNA (bDNA) assay, reached a peak at 2 weeks postinoculation but dropped to below detectable levels by 12 weeks. At over 1.5 years postinoculation, all four juvenile macaques remain healthy and asymptomatic In a subsequent experiment, four neonatal rhesus macaques were given SIVmac-M4 intravenously. These animals exhibited high levels of viremia in the acute phase (2 weeks postinoculation) but are showing a relatively low viral load in the chronic phase of infection, with no clinical signs of disease for 1 year, These findings demonstrated that the intracytoplasmic domain of the transmembrane Env (Env-TM) is a Locus for attenuation in rhesus macaques.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available