Human TRIM5α mediated restriction of different HIV-1 subtypes and Lv2 sensitive and insensitive HIV-2 variants

Kaumanns, Patrick; Hagmann, Isabel; Dittmar, Matthias T.

doi:10.1186/1742-4690-3-79

Cited by 15 publications

(5 citation statements)

References 25 publications

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“…The HEK 293T cells used to produce the pseudovirus in our screen do not express APOBECs [ 6 ] so identification of these proteins was not expected. Neither did we identify TRIM5α because it is a species specific restriction factor and the human protein does not significantly affect HIV-1 [ 7 , 31 ]. Since the screen was completed two other factors have been reported; p21 acts during reverse transcription and is active in stem cells, macrophages and CD4+ lymphocytes [ 9 , 10 , 32 ] while SAMHD1 expression is confined to dendritic and myeloid lineage cells [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

A whole genome screen for HIV restriction factors

et al. 2011

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BackgroundUpon cellular entry retroviruses must avoid innate restriction factors produced by the host cell. For human immunodeficiency virus (HIV) human restriction factors, APOBEC3 (apolipoprotein-B-mRNA-editing-enzyme), p21 and tetherin are well characterised.ResultsTo identify intrinsic resistance factors to HIV-1 replication we screened 19,121 human genes and identified 114 factors with significant inhibition of infection. Those with a known function are involved in a broad spectrum of cellular processes including receptor signalling, vesicle trafficking, transcription, apoptosis, cross-nuclear membrane transport, meiosis, DNA damage repair, ubiquitination and RNA processing. We focused on the PAF1 complex which has been previously implicated in gene transcription, cell cycle control and mRNA surveillance. Knockdown of all members of the PAF1 family of proteins enhanced HIV-1 reverse transcription and integration of provirus. Over-expression of PAF1 in host cells renders them refractory to HIV-1. Simian Immunodeficiency Viruses and HIV-2 are also restricted in PAF1 expressing cells. PAF1 is expressed in primary monocytes, macrophages and T-lymphocytes and we demonstrate strong activity in MonoMac1, a monocyte cell line.ConclusionsWe propose that the PAF1c establishes an anti-viral state to prevent infection by incoming retroviruses. This previously unrecognised mechanism of restriction could have implications for invasion of cells by any pathogen.

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Section: Discussionmentioning

confidence: 99%

A whole genome screen for HIV restriction factors

et al. 2011

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“…The reason for this lies in high market shares of low nickel‐containing austenitic stainless steels (Cr‐Mn grades) in India and China. While the global share of these grades was between 5% and 10%, they accounted for up to 20% of China's and 80% of India's stainless steel production (Kaumanns 2011). The manganese and copper contained in these grades pose a challenge at end of life if they are not kept separate from other austenitic grades.…”

Section: Discussionmentioning

confidence: 99%

Comparing Growth Rates of Nickel and Stainless Steel Use in the Early 2000s

Reck¹,

Rotter²

2012

J of Industrial Ecology

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Summary This study introduces the 2005 life cycle data for nickel in 50 countries and presents a comparative analysis of the 2000 and 2005 nickel and stainless steel cycles for these countries. The life cycles of the two metals are linked by nickel's role as a major alloying element in most stainless steels. Between 2000 and 2005, the global use of both metals grew, driven by China's extraordinary growth and despite the fact that many industrialized countries decreased their metal use during that time. China's and India's growth of stainless steel use was greater than that of nickel use, a result of price‐driven substitution away from nickel‐containing stainless steels. The intensity of use (IU) in industrialized countries is about 30 to 50 kilograms (kg) nickel/million U.S. dollars (USD), and 300 to 500 kg stainless steel/million USD. High‐income countries decreased their IU of both metals between 2000 and 2005, while low‐ and medium‐income countries increased their IU of stainless steel. At the per capita level, average industrialized countries use about 1 kg of nickel and 11 kg of stainless steel. Were China's and India's projected urban areas in 2025 to use similar amounts of the two metals, they alone would require the equivalent of global nickel production in 2000, and 200% of the world's stainless steel production in 2005. In China, substantial nickel and stainless steel end‐of‐life flows will arise between 2015 and 2020, and efficient collection and separation systems should be prepared now to maximize the potential environmental and resource benefits of recycling.

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“…Several correlates to restriction for MCR and MCN have been identified. The restricted MCR HIV-2 and the unrestricted MCN HIV-2 differ in gag and env sequences, with both genes playing a key role in determining Lv2 sensitivity ( 128 , 131 ). Specifically, in terms of the role of capsid, a single amino acid at position 73 in CA (Gag 207) confers sensitivity and resistance to Lv2 ( 128 ).…”

Section: Unknown Capsid-dependent Restrictionsmentioning

confidence: 99%

“…Second, the Lv2 restriction can be overcome by VSV-G pseudotyping, which bypasses receptor-mediated fusion and instead causes virus entry via an endocytic pathway ( 132 ), whereas TRIM5α restriction is not affected by VSV-G pseudotyping ( 128 , 130 ). Finally, the I73V CA mutant (Gag I207V) is not sensitive to Lv2 restriction but is susceptible to restriction by TRIM5α ( 131 , 133 ).…”

Section: Unknown Capsid-dependent Restrictionsmentioning

confidence: 99%

Capsid-dependent lentiviral restrictions

Twentyman,

Emerman,

Ohainle

2024

J Virol

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Host antiviral proteins inhibit primate lentiviruses and other retroviruses by targeting many features of the viral life cycle. The lentiviral capsid protein and the assembled viral core are known to be inhibited through multiple, directly acting antiviral proteins. Several phenotypes, including those known as Lv1 through Lv5 , have been described as cell type-specific blocks to infection against some but not all primate lentiviruses. Here we review important features of known capsid-targeting blocks to infection together with several blocks to infection for which the genes responsible for the inhibition still remain to be identified. We outline the features of these blocks as well as how current methodologies are now well suited to find these antiviral genes and solve these long-standing mysteries in the HIV and retrovirology fields.

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Human TRIM5α mediated restriction of different HIV-1 subtypes and Lv2 sensitive and insensitive HIV-2 variants

Abstract: In order to characterize the antiviral activity of human TRIM5α in more detail human derived indicator cell lines over expressing wild type human TRIM5α were generated and challenged with

Cited by 15 publications

References 25 publications

A whole genome screen for HIV restriction factors

A whole genome screen for HIV restriction factors

Comparing Growth Rates of Nickel and Stainless Steel Use in the Early 2000s

Capsid-dependent lentiviral restrictions

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