Retroviral Integrase: Then and Now

Andrake, Mark D.; Skalka, Anna Marie

doi:10.1146/annurev-virology-100114-055043

Cited by 26 publications

(17 citation statements)

References 148 publications

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“…The later hypothesis was not supported by this study, as genes 2L and 67L of group I isolates from different species were identical, while these genes originating from the same host species sometimes differed. For CMTV NL group III, truncations in two other functional genes were observed; p31K, a delayed early gene involved in transcriptional DNA/RNA synthesis 33 , and a putative integrase-like gene, which permits the incorporation of viral genetic material into host DNA 34 . Whether those, or other not yet annotated, genes account for suspected attenuation or reduced virulence of CMTV-NL group III ranaviruses, warrants further research.…”

Section: Discussionmentioning

confidence: 99%

Ranavirus genotypes in the Netherlands and their potential association with virulence in water frogs ( Pelophylax spp.)

Saucedo

Hughes

Sluijs³

et al. 2018

Emerging Microbes & Infections

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Ranaviruses are pathogenic viruses for poikilothermic vertebrates worldwide. The identification of a common midwife toad virus (CMTV) associated with massive die-offs in water frogs (Pelophylax spp.) in the Netherlands has increased awareness for emerging viruses in amphibians in the country. Complete genome sequencing of 13 ranavirus isolates collected from ten different sites in the period 2011–2016 revealed three CMTV groups present in distinct geographical areas in the Netherlands. Phylogenetic analysis showed that emerging viruses from the northern part of the Netherlands belonged to CMTV-NL group I. Group II and III viruses were derived from the animals located in the center-east and south of the country, and shared a more recent common ancestor to CMTV-amphibian associated ranaviruses reported in China, Italy, Denmark, and Switzerland. Field monitoring revealed differences in water frog host abundance at sites where distinct ranavirus groups occur; with ranavirus-associated deaths, host counts decreasing progressively, and few juveniles found in the north where CMTV-NL group I occurs but not in the south with CMTV-NL group III. Investigation of tandem repeats of coding genes gave no conclusive information about phylo-geographical clustering, while genetic analysis of the genomes revealed truncations in 17 genes across CMTV-NL groups II and III compared to group I. Further studies are needed to elucidate the contribution of these genes as well as environmental variables to explain the observed differences in host abundance.

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Section: Discussionmentioning

confidence: 99%

Ranavirus genotypes in the Netherlands and their potential association with virulence in water frogs ( Pelophylax spp.)

Saucedo

Hughes

Sluijs³

et al. 2018

Emerging Microbes & Infections

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“…The retrovirus integrase (IN) 3 is responsible for the concerted integration of linear viral cDNA ends into the host DNA genome and has multiple auxiliary roles including reverse transcription and virus particle maturation (for reviews, see Refs. [1][2][3][4]. Reverse transcription of the viral RNA in virus-infected cells results in the cytoplasmic preintegration complex (PIC).…”

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confidence: 99%

A C-terminal “Tail” Region in the Rous Sarcoma Virus Integrase Provides High Plasticity of Functional Integrase Oligomerization during Intasome Assembly

Pandey

Bera

Shi

et al. 2017

Journal of Biological Chemistry

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The retrovirus integrase (IN) inserts the viral cDNA into the host DNA genome. Atomic structures of five different retrovirus INs complexed with their respective viral DNA or branched viral/target DNA substrates have indicated these intasomes are composed of IN subunits ranging from tetramers, to octamers, or to hexadecamers. IN precursors are monomers, dimers, or tetramers in solution. But how intasome assembly is controlled remains unclear. Therefore, we sought to unravel the functional mechanisms in different intasomes. We produced kinetically stabilized Rous sarcoma virus (RSV) intasomes with human immunodeficiency virus type 1 strand transfer inhibitors that interact simultaneously with IN and viral DNA within intasomes. We examined the ability of RSV IN dimers to assemble two viral DNA molecules into intasomes containing IN tetramers in contrast to one possessing IN octamers. We observed that the last 18 residues of the C terminus ("tail" region) of IN (residues 1-286) determined whether an IN tetramer or octamer assembled with viral DNA. A series of truncations of the tail region indicated that these 18 residues are critical for the assembly of an intasome containing IN octamers but not for an intasome containing IN tetramers. The C-terminally truncated IN (residues 1-269) produced an intasome that contained tetramers but failed to produce an intasome with octamers. Both intasomes have similar catalytic activities. The results suggest a high degree of plasticity for functional multimerization and reveal a critical role of the C-terminal tail region of IN in higher order oligomerization of intasomes, potentially informing future strategies to prevent retroviral integration.

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“…RMERV pol contained PR and RT active-site motifs (D 16 TG and Y 332 VDD 335 , respectively), an IN Zn 2ϩ -chelating HHCC domain (H 938 GPTH.CPVC 975 ), and a catalytic core domain (D 1155 .E 1192 ) ( Fig. 3B) (36,44).…”

Section: Resultsmentioning

confidence: 99%

Viral Discovery in the Invasive Australian Cane Toad (Rhinella marina) Using Metatranscriptomic and Genomic Approaches

Russo

Eden

Tuipulotu

et al. 2018

J Virol

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Cane toads are a notorious invasive species, inhabiting over 1.2 million km of Australia and threatening native biodiversity. The release of pathogenic cane toad viruses is one possible biocontrol strategy yet is currently hindered by the poorly described cane toad virome. Metatranscriptomic analysis of 16 cane toad livers revealed the presence of a novel and full-length picornavirus, Rhimavirus A (RhiV-A), a member of a reptile- and amphibian-specific cluster of the basal to the-like group. In the combined liver transcriptome, we also identified a complete genome sequence of a distinct epsilonretrovirus, Rhinella marina endogenous retrovirus (RMERV). The recently sequenced cane toad genome contains 8 complete RMERV proviruses as well as 21 additional truncated insertions. The oldest full-length RMERV provirus was estimated to have inserted 1.9 million years ago (MYA). To screen for these viral sequences in additional toads, we analyzed publicly available transcriptomes from six diverse Australian locations. RhiV-A transcripts were identified in toads sampled from three locations across 1,000 km of Australia, stretching to the current Western Australia (WA) invasion front, while RMERV transcripts were observed at all six sites. Finally, we scanned the cane toad genome for nonretroviral endogenous viral elements, finding three sequences related to small DNA viruses in the family This shows ancestral circoviral infection with subsequent genomic integration. The identification of these current and past viral infections enriches our knowledge of the cane toad virome, an understanding of which will facilitate future work on infection and disease in this important invasive species. Cane toads are poisonous amphibians that were introduced to Australia in 1935 for insect control. Since then, their population has increased dramatically, and they now threaten many native Australian species. One potential method to control the population is to release a cane toad virus with high mortality rates, yet few cane toad viruses have been characterized. This study samples cane toads from different Australian locations and uses an RNA sequencing and computational approach to find new viruses. We report novel complete picornavirus and retrovirus sequences that were genetically similar to viruses infecting frogs, reptiles, and fish. Using data generated in other studies, we show that these viral sequences are present in cane toads from distinct Australian locations. Three sequences related to circoviruses were also found in the toad genome. The identification of new viral sequences will aid future studies that investigate their prevalence and potential as agents for biocontrol.

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Retroviral Integrase: Then and Now

Cited by 26 publications

References 148 publications

Ranavirus genotypes in the Netherlands and their potential association with virulence in water frogs ( Pelophylax spp.)

Ranavirus genotypes in the Netherlands and their potential association with virulence in water frogs ( Pelophylax spp.)

A C-terminal “Tail” Region in the Rous Sarcoma Virus Integrase Provides High Plasticity of Functional Integrase Oligomerization during Intasome Assembly

Viral Discovery in the Invasive Australian Cane Toad (Rhinella marina) Using Metatranscriptomic and Genomic Approaches

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