Influence of
            <i>gag</i>
            on Human Immunodeficiency Virus Type 1 Species-Specific Tropism

Ikeda, Yasuhiro; Ylinen, Laura M. J.; Kahar-Bador, Maria; Towers, Greg J.

doi:10.1128/jvi.78.21.11816-11822.2004

Cited by 87 publications

(98 citation statements)

References 47 publications

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“…The close relatedness between sheep and goats is consistent with the ability of sheep (VMV) and goat (CAEV) lentiviruses to infect both ruminant species (8,32). The high variability of both PRYSPRY (6, 34; this work) and CA of SRLV (7,26) may account for the evolution of both virus and host, involving TRIM5␣ and CA interactions, as described for primate lentiviruses (11,28,34,38). Natural selection in ovine and caprine sequences was determined by estimating (ratio of the rate of nonsynonymous substitutions, dN, to synonymous substitutions, Additional RNA species (6 from a total of 3 sheep) were identified that had a stop codon at residue 347 compared to the full ovine protein TRIM5␣ (OvT5␣), resulting in a reduced number of exons and elongated noncoding sequences at the 3= end, a structure similar to that of human TRIM5␥ (2) (Fig.…”

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confidence: 48%

mentioning

confidence: 99%

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Ovine TRIM5α Can Restrict Visna/Maedi Virus

Jáuregui

Crespo

Glaria

et al. 2012

J Virol

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The restrictive properties of tripartite motif-containing 5 alpha (TRIM5␣) from small ruminant species have not been explored. Here, we identify highly similar TRIM5␣ sequences in sheep and goats. Cells transduced with ovine TRIM5␣ effectively restricted the lentivirus visna/maedi virus DNA synthesis. Proteasome inhibition in cells transduced with ovine TRIM5␣ restored restricted viral DNA synthesis, suggesting a conserved mechanism of restriction. Identification of TRIM5␣ active molecular species may open new prophylactic strategies against lentiviral infections.S mall ruminant lentiviruses (SRLV), including visna/maedi virus (VMV) and caprine encephalitis virus (CAEV), are widespread in sheep and goats, causing a slow progressive disease. Since neither treatment nor efficient vaccines are available, infection is commonly controlled by early diagnosis and culling (23). Recently, the study of host cell restriction factors interfering with the retroviral life cycle, such as the tripartite motif-containing 5 (TRIM5) protein, has gained interest (10, 37). TRIM5 family members bear a RING-B-box-coiled-coil structure consisting of an N-terminal RING domain (with E3 ubiquitin ligase activity), a B-box domain, and a coiled-coil domain (19). The TRIM5␣ isoform, which is active against retroviruses, contains a C-terminal PRYSPRY domain that binds retroviral capsid CA (12,20,35). This interaction, involving amino acid 332 of TRIM5␣ in humans (15) and 334 in monkeys, may explain the high relative rates of nonsynonymous changes of the primate TRIM5␣ gene (13). TRIM5␣ has been described in primates and several mammals (3, 6, 30, 33, 41) but not in sheep or goats, both of which are infected by SRLV, their own lentivirus. This study aimed to identify and characterize the ovine and caprine TRIM5␣ proteins and explore the possible restrictive role of ovine TRIM5␣ on VMV infection.First, we cloned and sequenced ovine and caprine TRIM5␣ cDNA sequences. For this, total RNA from ovine skin fibroblasts (SF), bronchoalveolar lavage (BAL) fluid, or lung tissue obtained from domestic sheep of the Assaf (n ϭ 3), Churra (n ϭ 2), and Rasa Aragonesa (n ϭ 4) breeds was purified using TRIzol (Invitrogen) passed through RNeasy minikit columns (Qiagen), before being reverse transcribed with SuperScript II (Invitrogen) using an oligo(dT) primer according to the manufacturer's instructions. To clone the caprine counterpart, cDNA from peripheral blood mononuclear cells (PBMC) from goats of the Roccaverano (n ϭ 1) and Murciano-Granadina (n ϭ 2) breeds was used. These cDNAs were employed as the PCR template using Phusion high-fidelity DNA polymerase (Finnzymes) with the forward primer TrimEXNFw (5=-TGCA CCTCGAGATGGCTTCAGGAATCCTG-3=, XhoI site underlined) and the reverse primer PJ2 (5=-GATCCGGGCCCTCAAC AGCTTGGTGAGC-3=, ApaI site underlined) following standard thermal profiles. Amplified products were cloned into the TOPO Blunt vector (Invitrogen) as a shuttle/sequencing vector, yielding a total of 12 ovine and 5 caprine independent sequences. Four ov...

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supporting

confidence: 48%

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confidence: 99%

Ovine TRIM5α Can Restrict Visna/Maedi Virus

Jáuregui

Crespo

Glaria

et al. 2012

J Virol

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“…In humans, the HIV-1 infectivity is enhanced by the interaction of CypA with the capsid (29,30). On the contrary, in other primates, CypA interferes with the viral infection by enhancing the activity of the restriction factors TRIM5α and TRIM-Cyp (31,32).…”

Section: Discussionmentioning

confidence: 99%

Dynamic allostery governs cyclophilin A–HIV capsid interplay

Hou

Zhang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

153

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Host factor protein Cyclophilin A (CypA) regulates HIV-1 viral infectivity through direct interactions with the viral capsid, by an unknown mechanism. CypA can either promote or inhibit viral infection, depending on host cell type and HIV-1 capsid (CA) protein sequence. We have examined the role of conformational dynamics on the nanosecond to millisecond timescale in HIV-1 CA assemblies in the escape from CypA dependence, by magic-angle spinning (MAS) NMR and molecular dynamics (MD). Through the analysis of backbone 1H-15N and 1H-13C dipolar tensors and peak intensities from 3D MAS NMR spectra of wild-type and the A92E and G94D CypA escape mutants, we demonstrate that assembled CA is dynamic, particularly in loop regions. The CypA loop in assembled wild-type CA from two strains exhibits unprecedented mobility on the nanosecond to microsecond timescales, and the experimental NMR dipolar order parameters are in quantitative agreement with those calculated from MD trajectories. Remarkably, the CypA loop dynamics of wild-type CA HXB2 assembly is significantly attenuated upon CypA binding, and the dynamics profiles of the A92E and G94D CypA escape mutants closely resemble that of wild-type CA assembly in complex with CypA. These results suggest that CypA loop dynamics is a determining factor in HIV-1's escape from CypA dependence.

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“…17 and involves determinants present in the N-terminal domain of the capsid proteins that constitute the retroviral outer core structure. [18][19][20] After this initial contact, progression of the retroviral life cycle is impeded through several mechanisms. Viral cores seem to undergo accelerated uncoating, as evidenced by the disappearance of capsid in particulate form.…”

Section: Introductionmentioning

confidence: 99%