Restriction of multiple divergent retroviruses by Lv1 and Ref1

Hatziioannou, Théodora

doi:10.1093/emboj/cdg042

Cited by 220 publications

(221 citation statements)

References 52 publications

Supporting

Mentioning

217

Contrasting

Order By: Relevance

“…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).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Ovine TRIM5α Can Restrict Visna/Maedi Virus

Jáuregui

Crespo

Glaria

et al. 2012

J Virol

View full text Add to dashboard Cite

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...

show abstract

mentioning

confidence: 99%

“…In addition, we tested the restrictive role of OvT5 against VSV-G-pseudotyped HIV-2 viral vectors encoding green fluorescent protein (GFP), prepared by Fugene-6 transfection of 293T cells as described previously (10). We infected OvT5-MDTF cells and quantified infection at 48 h by measuring GFP expression using flow cytometry (BD FACScalibur).…”

mentioning

confidence: 99%

Ovine TRIM5α Can Restrict Visna/Maedi Virus

Jáuregui

Crespo

Glaria

et al. 2012

J Virol

View full text Add to dashboard Cite

show abstract

“…Uncoating events are likely to be relevant to HIV-1 tropism restrictions in cells of some nonhuman primate species, given the substantial reduction in reverse transcription products detected in newly infected cells (2,15,29). Thus, although HIV-1 entry into cells of several Old World monkey species is efficiently supported by simian CD4 and chemokine coreceptors (14,35), HIV-1 infection of these cells is restricted at a postentry step (2,3,15,28,31,45). Old World monkeys are natural hosts for SIV mac , which is not susceptible to postentry restrictions in these cells (16,30,31).…”

mentioning

confidence: 99%

Binding and Susceptibility to Postentry Restriction Factors in Monkey Cells Are Specified by Distinct Regions of the Human Immunodeficiency Virus Type 1 Capsid

Owens

Song

Perron

et al. 2004

J Virol

114

118

View full text Add to dashboard Cite

In cells of Old World and some New World monkeys, dominant factors restrict human immunodeficiency virus type 1 (HIV-1) infections after virus entry. The simian immunodeficiency virus SIV mac is less susceptible to these restrictions, a property that is determined largely by the viral capsid protein. For this study, we altered exposed amino acid residues on the surface of the HIV-1 capsid, changing them to the corresponding residues found on the SIV mac capsid. We identified two distinct pathways of escape from early, postentry restriction in monkey cells. One set of mutants that were altered near the base of the cyclophilin A-binding loop of the N-terminal capsid domain or in the interdomain linker exhibited a decreased ability to bind the restricting factor(s). Consistent with the location of this putative factor-binding site, cyclophilin A and the restricting factor(s) cooperated to achieve the postentry block. A second set of mutants that were altered in the ridge formed by helices 3 and 6 of the N-terminal capsid domain efficiently bound the restricting factor(s) but were resistant to the consequences of factor binding. These results imply that binding of the simian restricting factor(s) is not sufficient to mediate the postentry block to HIV-1 and that SIV mac capsids escape the block by decreases in both factor binding and susceptibility to the effects of the factor(s).

show abstract

“…Since the receptor for VSVg is a membrane phospholipid 26 and for LCMV it is a-dystroglycan, 27 the restriction observed must occur at some stage after entry. Therefore, the low permissiveness of HVS-T cells may be due either to intrinsic cellular factors present in T cells 28,29 or to the possible expression of HVS latent genes that might interfere with lentiviral vector transduction. In our case, viral interferences are unlikely since HVS cells are permissive to HIV-1 infection 30,31 and the expression of the HVS latent gene stpC enhances HIV-1 replication.…”

Section: Discussionmentioning

confidence: 99%

“…32 If HVS immortalization does not block HIV replication but rather enhances it, T-cell factors must be primarily involved in explaining the relatively low permissiveness of HIV-1 vectors in HVS-T cells. In fact, T lymphocytes have several mechanisms that are capable of inhibiting HIV-1 replication 28,29 and so it is likely that the restriction observed results from a behavior mirroring primary T cells. This would explain why the lentiviral vector acts equally well or even more efficiently on HVS-T cells than it does on primary T cells ( Figure 5).…”

Section: Discussionmentioning

confidence: 99%