Replication of HIV-1 and N-tropic murine leukemia virus (N-MLV) is restricted in a number different primate cells. In some cell lines, cross-saturation experiments suggest that the two viruses are interacting with same restriction factor. Recently, Trim5alpha protein from rhesus monkey was found to restrict HIV-1. We have confirmed this result shown African green Vero CV-1, also restricts addition, we show human, rhesus, can N-MLV. By using panel MLV capsid mutants, subtle differences...

Lv1 restriction of HIV-1 in the cells Old World monkeys is associated with expression Trim5 gene. Uniquely, owl monkey kidney cells, dependent on ability incoming viral capsid protein to bind cyclophilin A (CypA). Cloning gene now reveals presence an inserted CypA pseudogene within intron 7 This insertion results formation a chimeric Trim5-CypA transcript. Transfer cDNA corresponding this transcript into human confers cyclosporin A-sensitive resistance infection. The factor appears be...

Restriction factors (RFs) form important components of host defenses to retroviral infection. The Fv1, Trim5α, and TrimCyp RFs contain N-terminal dimerization C-terminal specificity domains that target assembled capsid (CA) proteins enclosing the viral core. However, molecular detail interaction between their CA targets is unknown. Therefore, we have determined crystal structure B-box coiled-coil (BCC) region from Trim5α used small-angle X-ray scattering examine solution BCC, domain Fv1...

SARS-CoV-2 is a betacoronavirus and the etiological agent of COVID-19, devastating infectious disease. Due to its far-reaching effect on human health, there an urgent growing need understand viral molecular biology interaction with host cell. encodes 9 predicted accessory proteins, which are presumed be dispensable for in vitro replication, most likely having role modulating cell environment aid replication. Here we show that ORF6 protein interacts cellular Rae1 inhibit production by...

ABSTRACT Recent studies have revealed the contribution of TRIM5α to retrovirus restriction in cells from a variety primate species. consists tripartite motif (the RBCC domain) followed by B30.2 domain. The domain is thought be involved determination specificity and contains three variable regions. To investigate relationship between phylogeny specificity, series chimeric consisting human various primates was constructed. These constructs showed profiles largely consistent with origin...

Xenotropic murine leukemia virus-related virus (XMRV) is a recently discovered gammaretrovirus that has been linked to prostate cancer and chronic fatigue syndrome. This therefore an important potential human pathogen and, as such, it essential understand its host cell tropism. Intriguingly, infectious recovered from patient-derived peripheral blood mononuclear cells. These cells express several antiviral restriction factors are capable of inhibiting the replication wide range retroviruses,...

Fv1 is the prototypic restriction factor that protects against infection by murine leukemia virus (MLV). It was first identified in cells were derived from laboratory mice and found to be homologous gag gene of an endogenous retrovirus (ERV). To understand evolution host its retroviral origins, Fv1s wild isolated characterized. Most these possess intact open reading frames but not all restricted N-, B-, NR-or NB-tropic MLVs, suggesting other viruses could have played a role selection gene....

ABSTRACT The Trim5α protein from several primates restricts retroviruses in a capsid (CA)-dependent manner. In owl monkeys, the B30.2 domain of Trim5 has been replaced by cyclophilin A (CypA) following retrotransposition. Restriction human immunodeficiency virus type 1 (HIV-1) resulting Trim5-CypA fusion depends on CA binding to CypA, suggesting both that might be involved and tripartite R ING motif, B -BOX, c oiled oil (RBCC) motif can function independently restriction. To investigate...

Tripartite motif (TRIM)5 alpha has recently been identified as a host restriction factor that the ability to block infection by certain retroviruses in species-dependent manner. One interesting feature of this protein is it localized distinct cytoplasmic clusters designated bodies. The potential role these bodies TRIM5 function remains be defined. By using fluorescent fusion proteins and live cell microscopy, we studied localization dynamics This analysis reveals are highly mobile,...

Foamy viruses (FVs) are unconventional retroviruses with a replication strategy that is significantly different from orthoretroviruses and bears some homology to of hepadnaviruses. Although cellular proteins, such as APOBEC3, have been reported block FVs, no restriction by Trim5alpha has described date. The sensitivity three FV isolates human-chimpanzee or prototypic (PFV), macaque (SFVmac), feline (FFV) origin variety primate Trim5alphas was therefore tested. PFV SFVmac were restricted most...

After entry into target cells, retroviruses encounter the host restriction factors such as Fv1 and TRIM5α. While it is clear that these retrovirus capsid proteins (CA), recognition remains poorly defined in absence of structural information. To better understand binding interaction between TRIM5α CA, we selected a panel novel N-tropic murine leukaemia virus (N-MLV) escape mutants by serial passage replication competent N-MLV rhesus macaque (rhTRIM5α)-positive cells using small percentage...

The retroviral restriction factor tripartite motif–containing 5α (Trim5α) acts during the early postentry stages of life cycle to block infection by a broad range retroviruses, disrupting reverse transcription and integration. mechanism this is poorly understood, but it has recently been suggested involve recruitment components autophagy machinery, including members mammalian autophagy-related 8 (ATG8) family involved in targeting proteins autophagosome. To better understand molecular...

ABSTRACT The specificity determinants for susceptibility to resistance by the Fv1 n and b alleles map amino acid 110 of murine leukemia virus CA protein. To study interaction between CA, we examined changes in resulting loss naturally occurring NB- NR-tropic viruses. A variety affecting tropism were identified, at positions 82, 92 95, 105, 114, 117, they all mapped apparent exterior virion-associated CA. These acids may form a binding surface Fv1.

Abstract Vpr is a conserved primate lentiviral accessory protein that induces cell cycle arrest in G2. The precise mechanism of this and its benefit to viral replication unknown. Here, we show addition G2 arrest, from HIV-1/SIVcpz HIV-2 lineages separately induce mitotic through the spindle assembly checkpoint, contrast other proteins only cause arrest. was mediated solely by ATR (ataxia telangiectasia Rad3 related) activity caused elevated cellular dNTP levels. required ATM...

Abstract SAMHD1 is an intracellular enzyme that specifically degrades deoxynucleoside triphosphates into component nucleoside and inorganic triphosphate. In myeloid-derived dendritic cells macrophages as well resting T-cells, blocks HIV-1 infection through this dNTP triphosphohydrolase activity by reducing the cellular pool to a level cannot support productive reverse transcription. We now show that, in addition direct effect on virus replication, manipulating can significantly enhance or...

Both exogenous and endogenous retroviruses have long been studied in mice, some of the earliest mouse studies focused on heritability genetic factors influencing permissivity resistance to infection. The prototypic retroviral restriction factor, Fv1, is now understood exhibit a degree control across multiple genera highly diverse within Mus To better understand age evolutionary history comprehensive survey Muroidea was conducted, allowing progenitor integration be dated ∼45 million years....

Murine leukemia virus is restricted in mouse cells lines by a host factor known as Fv1 and human cell Ref1. Genetic evidence indicates that these restriction factors target the capsid (CA) protein. Restriction can be overcome adding at high multiplicity of infection, indicating saturated. Cells preexposed to will allow infection second which would normally restricted. This phenomenon abrogation; it provides us with tool study interaction factors. We tested abilities several Gag processing...

The Spumaretrovirinae, or foamyviruses (FVs) are complex retroviruses that infect many species of monkey and ape. Although FV infection is apparently benign, trans-species zoonosis commonplace has resulted in the isolation Prototypic Foamy Virus (PFV) from human sources potential for germ-line transmission. Despite little sequence homology, orthoretroviral Gag proteins perform equivalent functions, including genome packaging, virion assembly, trafficking membrane targeting. In addition, PFV...

Lentiviruses, the genus of retrovirus that includes HIV-1, rarely endogenize. Some lemurs uniquely possess an endogenous lentivirus called PSIV ("prosimian immunodeficiency virus"). Thus, provide opportunity to study activity host defense factors, such as TRIM5α, in setting germ line invasion. We characterized activities TRIM5α proteins from two distant against exogenous retroviruses and a chimeric PSIV. gray mouse lemur, which carries its genome, exhibited narrowest restriction activity....

Summary: Pseudomonas alcaligenes NCIB 9867 (strain P25X), which grows on 2,5-xylenol and harbours the plasmid RP4, was mated with a plasmid-free derivative of putida 9869, strain RA713, cannot grow 2,5-xylenol. Some RA713 transconjugants, initially selected 2,5-xylenol, were found to carry RP4 plasmids that had acquired additional fragments (designated XIn) ranged in size from 2 kb approximately 26 kb. Instability DNA inserts RP4::XIn hybrid observed. The smallest insert present stable...