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Abstract
PHENOTYPIC AND ANTIGENIC PROPERTIES ASSOCIATED WITH PATHOGENIC R5-TROPIC SHIVSF162P3
HSU M, YANG D, CHENG-MAYER C
Objective: To characterize the properties of Env associated with increased pathogenicity of R5-specific SHIVSF162P3.
Materials and Methods: To examine the role of R5-specific envelopes in HIV-1 pathogenesis, SHIVSF162, a chimera consisting of the R5-tropic HIV-1SF162 env, tat, rev and vpu genes cloned into the pathogenic SIVmac239 was constructed. Upon serial passage of SHIVSF162 in vivo, increased replication of the virus was observed. The late passage virus, designated SHIVSF162P3, induced Simian AIDS (SAIDS) in naïve macaques and transmitted efficiently across mucosal barriers. In vitro infectivity, cytopathicity and neutralization studies were performed to identify properties of SHIVSF162P3 that may correlate with its increased virulence in vivo.
Results: Compare to parental SHIVSF162, SHIVSF162P3 replicates with faster kinetics and to slightly higher titers in rhesus PBMC. Replication of the pathogenic variant in human PBMCs however, appears to be attenuated. SHIVSF162P3 is also more cytopathic, and escapes neutralization with autologous sera. More importantly, SHIVSF162P3 is capable of productively infecting immature dendritic cells (DC) and transmits the virus more efficiently in DC/T cell conjugates than SHIVSF162.
Conclusions: Increased pathogenicity and mucosal transmissibility of SHIVSF162P3 are associated with enhanced envelope-determined properties such as replicative capacity, cytopathicity, neutralization escape and efficient infection of dentritic cells. Ongoing studies with molecular clones should clarify the role of these envelope functions in viral pathogenesis.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
72
Suggested Citation
"HSUM, et al.
PHENOTYPIC AND ANTIGENIC PROPERTIES ASSOCIATED WITH PATHOGENIC R5-TROPIC SHIVSF162P3.
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
72"
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