scholarly journals Generation of a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone, a derivative of SHIV-89.6

2016 ◽  
Vol 97 (5) ◽  
pp. 1249-1260 ◽  
Author(s):  
Yuki Ishida ◽  
Mai Yoneda ◽  
Hiroyuki Otsuki ◽  
Yuji Watanabe ◽  
Fumihiro Kato ◽  
...  
2000 ◽  
Vol 44 (5) ◽  
pp. 1127-1131 ◽  
Author(s):  
Nathalie Richard ◽  
Horacio Salomon ◽  
Robert Rando ◽  
Tarek Mansour ◽  
Terry L. Bowlin ◽  
...  

ABSTRACT Human immunodeficiency virus (HIV) type 1 (HIV-1) variants were selected for resistance to the (+) and (−) enantiomers of a novel nucleoside analogue, 2′-deoxy-3′-oxa-4′-thio-5-fluorocytidine (dOTFC), by use of the infectious molecular clone HIV HXB2D and the human T-cell line MT-4. The dOTFC-resistant variants that were selected were 10-fold less sensitive than wild-type virus, and cloning and sequencing of the complete reverse transcriptase (RT)-coding region identified the mutation M184V. Studies with mutated recombinant HXB2D virus confirmed the importance of the M184V mutation in conferring resistance to (−)dOTFC in MT-4 cells, although no difference in sensitivity was observed in primary cells. The M184V substitution also displayed decreased susceptibility to (+)dOTFC. Selection with (+)dOTFC also produced variants which were 10-fold more resistant than the wild type, and a novel mutation, D67G, was identified following cloning and sequencing of the RT genes. The D67G mutation was introduced into HXB2D by site-directed mutagenesis, and the data obtained confirmed the importance of this mutation in conferring resistance to both (+)dOTFC and (−)dOTFC. Mutated recombinant molecular clone HXB2D-D67G was further selected with (+)dOTFC, and three of six clones sequenced contained both the D67G and M184V mutations, while the other three of the six clones contained only the D67G mutation. Clinical isolates of HIV-1 which are (−) 2′-deoxy-3′-thiacytidine-resistant also displayed resistance to both (+)dOTFC and (−)dOTFC.


Virology ◽  
2000 ◽  
Vol 272 (1) ◽  
pp. 112-126 ◽  
Author(s):  
Coleen McCormick-Davis ◽  
Steven B. Dalton ◽  
David R. Hout ◽  
Dinesh K. Singh ◽  
Nancy E.J. Berman ◽  
...  

2018 ◽  
Vol 218 (9) ◽  
pp. 1447-1452 ◽  
Author(s):  
Ayub Ali ◽  
Hwee L Ng ◽  
Joel N Blankson ◽  
Dennis R Burton ◽  
Robert W Buckheit ◽  
...  

2004 ◽  
Vol 78 (24) ◽  
pp. 14066-14069 ◽  
Author(s):  
Ricky D. Grisson ◽  
Agnès-Laurence Chenine ◽  
Lan-Yu Yeh ◽  
Jun He ◽  
Charles Wood ◽  
...  

ABSTRACT Although human immunodeficiency virus type 1 (HIV-1) clade C continues to dominate the pandemic, only two infectious clade C proviral DNA clones have been described (N. Mochizuki, N. Otsuka, K. Matsuo, T. Shiino, A. Kojima, T. Kurata, K. Sakai, N. Yamamoto, S. Isomura, T. N. Dhole, Y. Takebe, M. Matsuda, and M. Tatsumi, AIDS Res. Hum. Retrovir. 15:1321-1324, 1999; T. Ndung'u, B. Renjifo, and M. Essex, J. Virol. 75:4964-4972, 2001). We have generated an infectious molecular clone of a pediatric clade C strain, HIV1084i, which was isolated from a Zambian infant infected either intrapartum or through breastfeeding. HIV1084i is an R5, non-syncytium-inducing isolate that bears all known clade C signatures; gag, pol, and env consistently mapped within clade C. Interestingly, gag resembled Asian isolates, whereas pol and env resembled African isolates, indicating that HIV1084i probably arose from an intraclade recombination. As a recently transmitted clade C strain, HIV1084i will be a useful vaccine development tool.


1998 ◽  
Vol 72 (4) ◽  
pp. 3248-3258 ◽  
Author(s):  
Christopher J. Miller ◽  
Marta Marthas ◽  
Jennifer Greenier ◽  
Ding Lu ◽  
Peter J. Dailey ◽  
...  

ABSTRACT We used the rhesus macaque model of heterosexual human immunodeficiency virus (HIV) transmission to test the hypothesis that in vitro measures of macrophage tropism predict the ability of a primate lentivirus to initiate a systemic infection after intravaginal inoculation. A single atraumatic intravaginal inoculation with a T-cell-tropic molecular clone of simian immunodeficiency virus (SIV), SIVmac239, or a dualtropic recombinant molecular clone of SIV, SIVmac239/1A11/239, or uncloned dualtropic SIVmac251 or uncloned dualtropic simian/human immunodeficiency virus (SHIV) 89.6-PD produced systemic infection in all rhesus macaques tested. However, vaginal inoculation with a dualtropic molecular clone of SIV, SIVmac1A11, resulted in transient viremia in one of two rhesus macaques. It has previously been shown that 12 intravaginal inoculations with SIVmac1A11 resulted in infection of one of five rhesus macaques (M. L. Marthas, C. J. Miller, S. Sutjipto, J. Higgins, J. Torten, B. L. Lohman, R. E. Unger, H. Kiyono, J. R. McGhee, P. A. Marx, and N. C. Pedersen, J. Med. Primatol. 21:99–107, 1992). In addition, SHIV HXBc2, which replicates in monkey macrophages, does not infect rhesus macaques following multiple vaginal inoculations, while T-cell-tropic SHIV 89.6 does (Y. Lu, P. B. Brosio, M. Lafaile, J. Li, R. G. Collman, J. Sodroski, and C. J. Miller, J. Virol. 70:3045–3050, 1996). These results demonstrate that in vitro measures of macrophage tropism do not predict if a SIV or SHIV will produce systemic infection after intravaginal inoculation of rhesus macaques. However, we did find that the level to which these viruses replicate in vivo after intravenous inoculation predicts the outcome of intravaginal inoculation with each virus.


2001 ◽  
Vol 75 (11) ◽  
pp. 4964-4972 ◽  
Author(s):  
Thumbi Ndung'u ◽  
Boris Renjifo ◽  
Max Essex

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) subtype C is now the predominant subtype in the global epidemic. This subtype is encountered in southern Africa and parts of Asia, where the epidemic is rapidly spreading. One possible explanation for these epidemiological observations is that this subtype has genetic characteristics that may contribute to its spread and/or pathogenic potential. In this report, we describe the construction of MJ4, an infectious chimeric molecular clone of HIV-1 subtype C that replicates in donor peripheral blood mononuclear cells and macrophages. We also tested this clone for its ability to use the chemokine receptors CCR1, CCR2b, CCR3, CXCR4, and CCR5 and found that the clone utilizes only CCR5 as the coreceptor for cell entry. The MJ4 clone will be useful in further biological and virological characterization of HIV-1 subtype C and will be an important tool in the continuing efforts to understand what may constitute protective immunity in HIV-1. The clone may also be used in experimental design of vaccine candidates that may be directed against HIV-1 subtype C.


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