Role of HIV-2 envelope in Lv2-mediated restriction

Reuter, Sandra; Kaumanns, Patrick; Buschhorn, Sabine B.; Dittmar, Matthias T.

doi:10.1016/j.virol.2004.11.025

Cited by 31 publications

(37 citation statements)

References 53 publications

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“…In addition, Lv2 was rescued by treatment with NH 4 Cl. Recently, Reuter et al reported that Lv2 restriction can be partially overcome with NH 4 Cl treatment (29). These authors conclude the involvement of a pHdependent route.…”

Section: Discussionmentioning

confidence: 91%

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An Envelope-Determined, pH-Independent Endocytic Route of Viral Entry Determines the Susceptibility of Human Immunodeficiency Virus Type 1 (HIV-1) and HIV-2 to Lv2 Restriction

Marchant¹,

Neil²,

Aubin³

et al. 2005

J Virol

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We identified a postentry restriction, termed Lv2, which determines the cellular tropism of two related human immunodeficiency virus type 2 (HIV-2) isolates and is dependent on the sequence of the capsid (CA) and envelope (Env) proteins. To explain the reliance on both CA and Env, we proposed that restrictive Envs deliver susceptible capsids to a compartment where Lv2 is active whereas nonrestrictive Envs deliver capsids into a compartment where Lv2 is either absent or less active. To test this model, we used compounds that affect endocytic pathways (ammonium chloride, bafilomycin A1, hypertonic sucrose) or lipid rafts (methyl-␤-cyclodextrin) to treat restrictive cells and show that restricted virus can be rescued from Lv2 if a lipid-raftdependent, pH-independent endocytic pathway is inhibited. Furthermore, viral entry into HeLa/CD4 cells containing a tailless CD4 receptor, located outside lipid rafts, was fully permissive. Finally, we show that a variety of primary HIV-1 and HIV-2 viruses are susceptible to Lv2. Thus, we show that the route of entry, determined by the viral envelope, can influence cellular tropism by avoiding intracellular blocks to infection.

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Section: Discussionmentioning

confidence: 91%

“…In addition to CA, we showed that changes in the envelope protein (Env) also overcome Lv2 (33). The Env contribution to Lv2 can be accounted for by a single amino acid change in the V1 domain (29). So far, viral Envs have not been implicated in the Lv1/Ref1 restriction (33).…”

mentioning

confidence: 91%

An Envelope-Determined, pH-Independent Endocytic Route of Viral Entry Determines the Susceptibility of Human Immunodeficiency Virus Type 1 (HIV-1) and HIV-2 to Lv2 Restriction

Marchant¹,

Neil²,

Aubin³

et al. 2005

J Virol

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“…64 pNL4-3, pNL-GFP, pMD-G, pCIG3N, pCIG3B, pCNCG, pDR8.9, pTRIP CMVÀGFP , pCL-Eco, pROD NefÀGFP , pSIV macÀGFP , pONY3.1 and pONY8.0 have all been extensively described before 44,[65][66][67][68][69][70][71][72] …”

Section: Cells and Plasmids Dnasmentioning

confidence: 99%

Generation of human TRIM5α mutants with high HIV-1 restriction activity

et al. 2010

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“…Here we show that REAF is a major component of the previously described restriction Lv2 (35,53,54). HIV chimeric viruses and mutants that delineate susceptible and resistant clones demonstrate that Lv2 and REAF are indistinguishable.…”

Section: Discussionmentioning

confidence: 53%

RNA-Associated Early-Stage Antiviral Factor Is a Major Component of Lv2 Restriction

Marno

O'Sullivan

Jones

et al. 2017

J Virol

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Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication in human cells is restricted at early postentry steps by host inhibitory factors. We previously described and characterized an early-phase restriction of HIV-1 and -2 replication in human cell lines, primary macrophages, and peripheral blood mononuclear cells. The restriction was termed lentiviral restriction 2 (Lv2). The viral determinants of Lv2 susceptibility mapped to the HIV-2 envelope (Env) and capsid (CA). We subsequently reported a whole-genome small interfering RNA screening for factors involved in HIV that identified RNA-associated early-stage antiviral factor (REAF). Using HIV-2 chimeras of susceptible and nonsusceptible viruses, we show here that REAF is a major component of the previously described Lv2 restriction. Further studies of the viral CA demonstrate that the CA mutation I73V (previously called I207V), a potent determinant for HIV-2, is a weak determinant of susceptibility for HIV-1. More potent CA determinants for HIV-1 REAF restriction were identified at P38A, N74D, G89V, and G94D. These results firmly establish that in HIV-1, CA is a strong determinant of susceptibility to Lv2/REAF. Similar to HIV-2, HIV-1 Env can rescue sensitive CAs from restriction. We conclude that REAF is a major component of the previously described Lv2 restriction.IMPORTANCE Measures taken by the host cell to combat infection drive the evolution of pathogens to counteract or sidestep them. The study of such virus-host conflicts can point to possible weaknesses in the arsenal of viruses and may lead to the rational design of antiviral agents. Here we describe our discovery that the host restriction factor REAF fulfills the same criteria previously used to describe lentiviral restriction (Lv2). We show that, like the HIV-2 CA, the CA of HIV-1 is a strong determinant of Lv2/REAF susceptibility. We illustrate how HIV counteracts Lv2/REAF by using an envelope with alternative routes of entry into cells. KEYWORDS Lv2, REAF, antiviral Infection of cells by human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) is initiated by binding of the viral envelope (Env) to CD4. Conformational changes in the viral Env expose a site that can interact with a chemokine receptor, either CXCR4 or CCR5, expressed at the cell surface of CD4 ϩ T cells and primary macrophages (1, 2). Viruses in general can enter cells through different routes, either directly at the plasma membrane (PM) or through a number of endocytic pathways (3). Influenza virus is a prototypical virus that enters cells through an endocytic route and requires the acid environment of the late endosome to trigger its fusion to and entry into cells. Since the mechanism of HIV fusion is pH independent (4), it has been widely assumed that HIV fuses at the PM (5-7). pH-independent endocytic entry has recently been observed (8-15) and is thus a possible mechanism of HIV entry; this, however, remains a topic of considerable controversy (16, 17). Regardless of the

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Role of HIV-2 envelope in Lv2-mediated restriction

Cited by 31 publications

References 53 publications

An Envelope-Determined, pH-Independent Endocytic Route of Viral Entry Determines the Susceptibility of Human Immunodeficiency Virus Type 1 (HIV-1) and HIV-2 to Lv2 Restriction

An Envelope-Determined, pH-Independent Endocytic Route of Viral Entry Determines the Susceptibility of Human Immunodeficiency Virus Type 1 (HIV-1) and HIV-2 to Lv2 Restriction

Generation of human TRIM5α mutants with high HIV-1 restriction activity

RNA-Associated Early-Stage Antiviral Factor Is a Major Component of Lv2 Restriction

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