Bilateral renal histiocytic sarcoma with disseminated lung involvement in a Siberian Forest Cat.

Case summary: A 5-year-old female neutered Siberian Forest Cat presented with a 7-day history of lethargy, hyporexia and weight loss. Abdominal ultrasonography revealed bilateral renal changes suggestive of neoplasia. Thoracic radiography documented diffuse pulmonary nodules. The cat was euthanased during diagnostic investigations. Histopathological assessment and immunohistochemical staining of post-mortem renal biopsies were consistent with a histiocytic lesion, most likely histiocytic sarcoma (HS). The lung lesions were suspected of representing disseminated disease. Relevance and novel information: HS is considered a rare neoplastic process in cats. This report describes a case of feline bilateral renal HS with suspected concomitant pulmonary involvement. A primary renal origin was suspected, with the lung lesions being a result of disseminated disease. Renal HS should be included as a differential diagnosis when renal ultrasonography reveals changes suggestive of neoplasia.

Computed tomographic findings in dogs with multiple myeloma.

BACKGROUND: Computed tomography (CT) is considered the first-line imaging modality for human patients with suspected multiple myeloma (MM). Recently the diagnostic criteria for human MM have been updated. OBJECTIVES: To describe and provide a baseline of the CT features and distribution of osseous lesions in dogs diagnosed with MM and to describe the change of initial osseous lesions after the start of treatment in a subset of dogs. METHODS: Single-centre, retrospective, descriptive, case series. Dogs were included when they met the updated MM criteria and if a staging CT was performed at the time of diagnosis and prior to initiation of treatment. When available, change of osseous lesions was assessed on serial imaging studies. RESULTS: Thirteen dogs met the inclusion criteria. All dogs had involvement of the axial skeleton and 9/13 (69%) had concurrent involvement of the appendicular skeleton. Large (≥1 cm), lytic, 'punched out' or expansile bony lesions and regions of permeative lysis were most common and mainly affected the vertebral column. Discrete intramedullary soft tissue attenuating lesions of the proximal appendicular skeleton were observed in 8/13 dogs (61%) and bilateral involvement of both humeri and femurs was seen in 4/9 dogs (44%). A subset of dogs underwent serial imaging and progressive replacement of the contrast-enhancing lesions with fat attenuating tissue was observed for all dogs, corresponding with clinical improvement. CONCLUSIONS: This case series provides a baseline knowledge of the initial and follow-up CT features in dogs diagnosed with MM based on updated criteria.

Tonsillar carcinoma in dogs: Treatment outcome and potential prognostic factors in 123 cases.

BACKGROUND: Tonsillar carcinomas are rarely reported in dogs. Information on outcome after treatment is sparse and prognosis is guarded to poor. HYPOTHESIS/OBJECTIVES: Assess treatment outcome and potential prognostic factors in a population of dogs with cytological or histopathological diagnosis of tonsillar carcinoma. ANIMALS: A total of 123 client-owned dogs with diagnosis of tonsillar carcinoma confirmed by cytology or histopathology. METHODS: Retrospective, multi-institutional study. Medical records of 12 institutions were reviewed from 2012 to 2021. RESULTS: Treatment included surgery, chemotherapy (conventional, tyrosine kinase inhibitors or metronomic chemotherapy), radiotherapy, nonsteroidal anti-inflammatory drugs (NSAIDs) or a combination of these. Surgery was performed in 68 cases, chemotherapy was administered in association with NSAIDs in 64 cases, NSAIDs were used alone in 14 cases and in association with surgery in 21 cases, whereas radiotherapy was used alone or in combination with surgery or chemotherapy in 20 cases. Overall survival time (OST) was 126 days (95% confidence interval [CI], 88-164). Significantly longer survival (P < .001) was seen in dogs without evidence of metastatic disease (median survival time, 381 days; 95% CI, 116-646). Other significant positive prognostic factors included absence of clinicals signs at presentation, surgery (tonsillectomy), use of adjuvant chemotherapy and use of NSAIDs. CONCLUSION AND CLINICAL IMPORTANCE: Asymptomatic dogs, those treated with surgery, those that received adjuvant chemotherapy, and those that received NSAIDs may have a better prognosis than previously expected, but overall survival remains short for dogs with tonsillar carcinoma.

rRNA expansion segment 7 in eukaryotes: from Signature Fold to tentacles.

The ribosomal core is universally conserved across the tree of life. However, eukaryotic ribosomes contain diverse rRNA expansion segments (ESs) on their surfaces. Sites of ES insertions are predicted from sites of insertion of micro-ESs in archaea. Expansion segment 7 (ES7) is one of the most diverse regions of the ribosome, emanating from a short stem loop and ranging to over 750 nucleotides in mammals. We present secondary and full-atom 3D structures of ES7 from species spanning eukaryotic diversity. Our results are based on experimental 3D structures, the accretion model of ribosomal evolution, phylogenetic relationships, multiple sequence alignments, RNA folding algorithms and 3D modeling by RNAComposer. ES7 contains a distinct motif, the 'ES7 Signature Fold', which is generally invariant in 2D topology and 3D structure in all eukaryotic ribosomes. We establish a model in which ES7 developed over evolution through a series of elementary and recursive growth events. The data are sufficient to support an atomic-level accretion path for rRNA growth. The non-monophyletic distribution of some ES7 features across the phylogeny suggests acquisition via convergent processes. And finally, illustrating the power of our approach, we constructed the 2D and 3D structure of the entire LSU rRNA of Mus musculus.

Caval chemodectoma in a cat.

Case summary: An 11-year-old male neutered domestic shorthair cat was presented with a 4-week history of an intermittent cough and dyspnoea. A pleural effusion was identified, which was confirmed as chyle. Echocardiography and CT revealed a 16 mm mass cranial to the heart, which was invading the cranial vena cava. Because of the location of the mass, it was assumed that chylothorax had developed as a result of direct disruption of the thoracic duct by the tumour or secondarily to central venous hypertension. An exploratory thoracotomy was performed, and the mass, which originated within the wall of the cranial vena cava, was excised with narrow gross margins. Histopathology and immunohistochemistry were consistent with a chemodectoma with residual tumour cells at the surgical margin. Given the residual microscopic disease, adjuvant treatment with toceranib phosphate was initiated. The cat remained well for the duration of treatment and was euthanased 31 months after diagnosis when CT identified recurrent pleural effusion, a heart base mass with cranial vena cava and azygos vein invasion. Relevance and novel information: Chemodectomas are rare in cats, with only 13 cases reported in the literature to date, and all were located in either the aortic or carotid body. The reported survival with partial resection and/or subtotal pericardiectomy was 13-19 months. Treatment of feline chemodectomas with toceranib phosphate has not been previously reported. To our knowledge, this is the first description of the surgical management of a feline vena cava chemodectoma, combined with adjuvant toceranib phosphate, resulting in a prolonged survival.

Tumours involving the retrobulbar space in cats: 37 cases.

OBJECTIVES: The aim of this multicentre retrospective study was to describe the clinical presentation, imaging findings, diagnosis and outcomes of cats with retrobulbar neoplasia. METHODS: A total of 37 cats that were diagnosed with retrobulbar neoplasia and underwent advanced imaging were recruited from searches of the clinical records of two referral hospitals. All cats had neoplasia confirmed via cytology or histopathology. Data relating to the signalment, presentation, results of investigations, treatment and outcome were recorded. A review of imaging studies was performed where possible. RESULTS: In total, 23 cases (62%) were presented with respiratory signs. Exophthalmos was the most common ophthalmological examination finding, present in 18 cases (49%). Thirty-two cases (86%) had secondary extension of neoplasia to the retrobulbar space (most commonly from the nasal cavities), present in 20 cases (54%), of which 12 were lymphoma. In cases where contrast was administered, 28/35 (80%) had contrast-enhancing masses. Orbital extension was detected in 21 cases (57%), exophthalmos in 22 (59%), globe deformation in 12 (32%) and local lymphadenomegaly in 22 (61%). In total, 36 (97%) retrobulbar tumours were malignant. Thoracic imaging, where it was performed, was concerning for metastasis in 8/25 cases (31%), with abdominal imaging suggestive of metastasis in 5/12 (42%). The most common diagnosis was lymphoma with 19 cases (51%), with nasal lymphoma representing 12 of these, followed by carcinoma in 10 (27%). The median survival time, for cases where death was recorded, was 85 days (range 1-263 days). CONCLUSIONS AND RELEVANCE: To the authors' knowledge, this is the largest study of neoplasia affecting the feline retrobulbar space. Retrobulbar tumours in cats are overwhelmingly malignant, and commonly due to secondary extension of tumours originating elsewhere. Lymphoma, particularly arising from the nasal cavities, was the most common cause. Cats presenting with signs suggestive of retrobulbar disease should be assessed for disease affecting any of the structures of the head.

Computed tomographic findings and clinical features in dogs with canine cutaneous lymphoma: 10 cases (2007-2018).

OBJECTIVE: To report clinical features, CT findings, treatment protocols, and outcomes for dogs in which canine cutaneous lymphoma (CCL) was diagnosed. ANIMALS: 10 client-owned dogs with CCL. PROCEDURES: Medical records of dogs in which a diagnosis of CCL had been made between September 2007 and July 2018 and in which CT had been performed prior to treatment were reviewed. All available CT studies were reviewed, and an anatomical reference system was developed to map observed lesions. Treatment protocols and patient outcomes were summarized. RESULTS: 14 CT examinations were performed on the 10 dogs, and 9 dogs had lesions consistent with CCL on CT images. Nodular lesions were present in 8 dogs, and cutaneous or subcutaneous mass lesions were seen in 3. Well-defined, diffusely distributed, contrast-enhancing, cutaneous or subcutaneous nodules were most common; mass lesions were more variable in appearance. Nine dogs had lymphadenopathy, with the mandibular and axillary lymph nodes most commonly affected. Four dogs had confirmed nodal involvement, and 4 had confirmed visceral involvement. Nine dogs received treatment with chemotherapy, and 5 had a complete response. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that dogs with CCL may have a wide spectrum of CT findings. Many of these lesions, including affected lymph nodes, would be unlikely to be detected clinically, suggesting that CT may be a useful modality to assess the severity of disease and for guiding selection of local versus systemic treatment.

Clinicopathological characteristics and prognostic factors for canine multicentric non-indolent T-cell lymphoma: 107 cases.

Canine lymphoma, as the most common haematopoietic malignancy, encompasses a group of heterogeneous diseases and even within the T-cell immunophenotype, differences in clinical presentation and responses to treatment exist. The aim of this retrospective study was to determine outcomes and prognostic factors of 107 dogs with multicentric non-indolent T-cell lymphoma (TCL) receiving lomustine-based (70%) and non-lomustine-based (30%) treatment. The majority were Labradors, Boxers, mixed-breed dogs and Dogue de Bordeaux. Eighty-six percent were substage b, 77% had mediastinal involvement, 15% had suspected bone marrow involvement and 12% had other extra-nodal sites of disease. The overall response rate to induction therapy was 80%; dogs receiving procarbazine in the induction protocol (P = .042), dogs with neutrophil concentration below 8.7 × 10e9 /L (P = .006) and mitotic rate below 10 per 5 high power field (P = .013), had greater response rates. Median progression-free survival (PFS) for the first remission was 105 days; lack of expression of CD3 on flow cytometry (P < .0001) and pretreatment with steroid (P = .012) were significantly associated with shorter PFS. Median overall survival time (OST) was 136 days; co-expression of CD79a (P = .002), lack of CD3 expression on flow cytometry, presence of anaemia (P = .007), and monocytopenia (P = .002) were predictive of shorter OST. Multicentric non-indolent TCL in dogs is an aggressive cancer with new possible prognostic factors.

Retroviral-like determinants and functions required for dimerization of Ty1 retrotransposon RNA.

During replication of long terminal repeat (LTR)-retrotransposons, their proteins and genome (g) RNA assemble into virus-like particles (VLPs) that are not infectious but functionally related to retroviral virions. Both virions and VLPs contain gRNA in a dimeric form, but contrary to retroviruses, little is known about how gRNA dimerization and packaging occurs in LTR-retrotransposons. The LTR-retrotransposon Ty1 from Saccharomyces cerevisiae is an informative model for studying LTR-retrotransposon and retrovirus replication. Using structural, mutational and functional analyses, we explored dimerization of Ty1 genomic RNA. We provide direct evidence that interactions of self-complementary PAL1 and PAL2 palindromic sequences localized within the 5'UTR are essential for Ty1 gRNA dimer formation. Mutations disrupting PAL1-PAL2 complementarity restricted RNA dimerization in vitro and Ty1 mobility in vivo. Although dimer formation and mobility of these mutants was inhibited, our work suggests that Ty1 RNA can dimerize via alternative contact points. In contrast to previous studies, we cannot confirm a role for PAL3, tRNAiMet as well as recently proposed initial kissing-loop interactions in dimer formation. Our data also supports the critical role of Ty1 Gag in RNA dimerization. Mature Ty1 Gag binds in the proximity of sequences involved in RNA dimerization and tRNAiMet annealing, but the 5' pseudoknot in Ty1 RNA may constitute a preferred Gag-binding site. Taken together, these results expand our understanding of genome dimerization and packaging strategies utilized by LTR-retroelements.

Eukaryotic Ribosomal Expansion Segments as Antimicrobial Targets.

Diversity in eukaryotic rRNA structure and function offers possibilities of therapeutic targets. Unlike ribosomes of prokaryotes, eukaryotic ribosomes contain species-specific rRNA expansion segments (ESs) with idiosyncratic structures and functions that are essential and specific to some organisms. Here we investigate expansion segment 7 (ES7), one of the largest and most variable expansions of the eukaryotic ribosome. We hypothesize that ES7 of the pathogenic fungi Candida albicans (ES7CA) could be a prototypic drug target. We show that isolated ES7CA folds reversibly to a native-like state. We developed a fluorescence displacement assay using an RNA binding fluorescent probe, F-neo. F-neo binds tightly to ES7CA with a Kd of 2.5 × 10-9 M but binds weakly to ES7 of humans (ES7HS) with a Kd estimated to be greater than 7 µM. The fluorescence displacement assay was used to investigate the affinities of a library of peptidic aminosugar conjugates (PAs) for ES7CA. For conjugates with highest affinities for ES7CA (NeoRH, NeoFH, and NeoYH), the lowest dose needed to induce mortality in C. albicans (minimum inhibitory concentration, MIC) was determined. PAs with the lowest MIC values were tested for cytotoxicity in HEK293T cells. Molecules with high affinity for ES7CA in vitro induce mortality in C. albicans but not in HEK293T cells. The results are consistent with the hypothesis that ESs represent useful targets for chemotherapeutics directed against eukaryotic pathogens.

A normal genetic variation modulates synaptic MMP-9 protein levels and the severity of schizophrenia symptoms.

Matrix metalloproteinase 9 (MMP-9) has recently emerged as a molecule that contributes to pathological synaptic plasticity in schizophrenia, but explanation of the underlying mechanisms has been missing. In the present study, we performed a phenotype-based genetic association study (PGAS) in > 1,000 schizophrenia patients from the Göttingen Research Association for Schizophrenia (GRAS) data collection and found an association between the MMP-9 rs20544 C/T single-nucleotide polymorphism (SNP) located in the 3'untranslated region (UTR) and the severity of a chronic delusional syndrome. In cultured neurons, the rs20544 SNP influenced synaptic MMP-9 activity and the morphology of dendritic spines. We demonstrated that Fragile X mental retardation protein (FMRP) bound the MMP-9 3'UTR We also found dramatic changes in RNA structure folding and alterations in the affinity of FMRP for MMP-9 RNA, depending on the SNP variant. Finally, we observed greater sensitivity to psychosis-related locomotor hyperactivity in Mmp-9 heterozygous mice. We propose a novel mechanism that involves MMP-9-dependent changes in dendritic spine morphology and the pathophysiology of schizophrenia, providing the first mechanistic insights into the way in which the single base change in the MMP-9 gene (rs20544) influences gene function and results in phenotypic changes observed in schizophrenia patients.

Structure of Ty1 Internally Initiated RNA Influences Restriction Factor Expression.

The long-terminal repeat retrotransposon Ty1 is the most abundant mobile genetic element in many Saccharomyces cerevisiae isolates. Ty1 retrotransposons contribute to the genetic diversity of host cells, but they can also act as an insertional mutagen and cause genetic instability. Interestingly, retrotransposition occurs at a low level despite a high level of Ty1 RNA, even though S. cerevisiae lacks the intrinsic defense mechanisms that other eukaryotes use to prevent transposon movement. p22 is a recently discovered Ty1 protein that inhibits retrotransposition in a dose-dependent manner. p22 is a truncated form of Gag encoded by internally initiated Ty1i RNA that contains two closely-spaced AUG codons. Mutations of either AUG codon compromise p22 translation. We found that both AUG codons were utilized and that translation efficiency depended on the Ty1i RNA structure. Structural features that stimulated p22 translation were context dependent and present only in Ty1i RNA. Destabilization of the 5' untranslated region (5' UTR) of Ty1i RNA decreased the p22 level, both in vitro and in vivo. Our data suggest that protein factors such as Gag could contribute to the stability and translational activity of Ty1i RNA through specific interactions with structural motifs in the RNA.

RNA-Puzzles Round III: 3D RNA structure prediction of five riboswitches and one ribozyme.

RNA-Puzzles is a collective experiment in blind 3D RNA structure prediction. We report here a third round of RNA-Puzzles. Five puzzles, 4, 8, 12, 13, 14, all structures of riboswitch aptamers and puzzle 7, a ribozyme structure, are included in this round of the experiment. The riboswitch structures include biological binding sites for small molecules (S-adenosyl methionine, cyclic diadenosine monophosphate, 5-amino 4-imidazole carboxamide riboside 5'-triphosphate, glutamine) and proteins (YbxF), and one set describes large conformational changes between ligand-free and ligand-bound states. The Varkud satellite ribozyme is the most recently solved structure of a known large ribozyme. All puzzles have established biological functions and require structural understanding to appreciate their molecular mechanisms. Through the use of fast-track experimental data, including multidimensional chemical mapping, and accurate prediction of RNA secondary structure, a large portion of the contacts in 3D have been predicted correctly leading to similar topologies for the top ranking predictions. Template-based and homology-derived predictions could predict structures to particularly high accuracies. However, achieving biological insights from de novo prediction of RNA 3D structures still depends on the size and complexity of the RNA. Blind computational predictions of RNA structures already appear to provide useful structural information in many cases. Similar to the previous RNA-Puzzles Round II experiment, the prediction of non-Watson-Crick interactions and the observed high atomic clash scores reveal a notable need for an algorithm of improvement. All prediction models and assessment results are available at http://ahsoka.u-strasbg.fr/rnapuzzles/.

Meeting report: Third Summer School on Innovative Approaches for Identification of Antiviral Agents (IAAASS).

The third Summer School on Innovative Approaches for Identification of Antiviral Agents (IAAASS) was held from September 28th to October 2nd, 2016 at the Sardegna Ricerche Research Park in Santa Margherita di Pula, Sardinia, Italy. The school brought together graduate students and postdoctoral fellows early in their careers with a faculty of internationally recognized experts, to encourage the sharing of knowledge and experience in virology research and drug development in an informal and interactive environment. The first IAAASS was held in Sardinia in 2012 and the second in 2014. The meetings provide a unique combination of plenary lectures on topics in virology, biochemistry, molecular modeling, crystallography and medicinal chemistry with small group sessions, in which students have the opportunity to ask questions and put forward their own ideas, and senior researchers offer advice, based on their own experience. This report summarizes presentations and presentations at the 3rd IAAASS.

Automated RNA 3D Structure Prediction with RNAComposer.

RNAs adopt specific structures to perform their activities and these are critical to virtually all RNA-mediated processes. Because of difficulties in experimentally assessing structures of large RNAs using NMR, X-ray crystallography, or cryo-microscopy, there is currently great demand for new high-resolution 3D structure prediction methods. Recently we reported on RNAComposer, a knowledge-based method for the fully automated RNA 3D structure prediction from a user-defined secondary structure. RNAComposer method is especially suited for structural biology users. Since our initial report in 2012, both servers, freely available at http://rnacomposer.ibch.poznan.pl and http://rnacomposer.cs.put.poznan.pl have been often visited. Therefore this chapter provides guidance for using RNAComposer and discusses points that should be considered when predicting 3D RNA structure. An application example presents current scope and limitations of RNAComposer.

Determinants of Genomic RNA Encapsidation in the Saccharomyces cerevisiae Long Terminal Repeat Retrotransposons Ty1 and Ty3.

Long-terminal repeat (LTR) retrotransposons are transposable genetic elements that replicate intracellularly, and can be considered progenitors of retroviruses. Ty1 and Ty3 are the most extensively characterized LTR retrotransposons whose RNA genomes provide the template for both protein translation and genomic RNA that is packaged into virus-like particles (VLPs) and reverse transcribed. Genomic RNAs are not divided into separate pools of translated and packaged RNAs, therefore their trafficking and packaging into VLPs requires an equilibrium between competing events. In this review, we focus on Ty1 and Ty3 genomic RNA trafficking and packaging as essential steps of retrotransposon propagation. We summarize the existing knowledge on genomic RNA sequences and structures essential to these processes, the role of Gag proteins in repression of genomic RNA translation, delivery to VLP assembly sites, and encapsidation.

Characterizing the functions of Ty1 Gag and the Gag-derived restriction factor p22/p18.

The long terminal repeat (LTR) and non-LTR retrotransposons comprise approximately half of the human genome, and we are only beginning to understand their influence on genome function and evolution. The LTR retrotransposon Ty1 is the most abundant mobile genetic element in the S. cerevisiae reference genome. Ty1 replicates via an RNA intermediate and shares several important structural and functional characteristics with retroviruses. However, unlike retroviruses Ty1 retrotransposition is not infectious. Retrotransposons integrations can cause mutations and genome instability. Despite the fact that S. cerevisiae lacks eukaryotic defense mechanisms such as RNAi, they maintain a relatively low copy number of the Ty1 retrotransposon in their genomes. A novel restriction factor derived from the C-terminal half of Gag (p22/p18) and encoded by internally initiated transcript inhibits retrotransposition in a dose-dependent manner. Therefore, Ty1 evolved a specific GAG organization and expression strategy to produce products both essential and antagonistic for retrotransposon movement. In this commentary we discuss our recent research aimed at defining steps of Ty1 replication influenced by p22/p18 with particular emphasis on the nucleic acid chaperone functions carried out by Gag and the restriction factor.

RNAComposer and RNA 3D structure prediction for nanotechnology.

RNAs adopt specific, stable tertiary architectures to perform their activities. Knowledge of RNA tertiary structure is fundamental to understand RNA functions beginning with transcription and ending with turnover. Contrary to advanced RNA secondary structure prediction algorithms, which allow good accuracy when experimental data are integrated into the prediction, tertiary structure prediction of large RNAs still remains a significant challenge. However, the field of RNA tertiary structure prediction is rapidly developing and new computational methods based on different strategies are emerging. RNAComposer is a user-friendly and freely available server for 3D structure prediction of RNA up to 500 nucleotide residues. RNAComposer employs fully automated fragment assembly based on RNA secondary structure specified by the user. Importantly, this method allows incorporation of distance restraints derived from the experimental data to strengthen the 3D predictions. The potential and limitations of RNAComposer are discussed and an application to RNA design for nanotechnology is presented.

The matrix domain contributes to the nucleic acid chaperone activity of HIV-2 Gag.

BACKGROUND: The Gag polyprotein is a multifunctional regulator of retroviral replication and major structural component of immature virions. The nucleic acid chaperone (NAC) activity is considered necessary to retroviral Gag functions, but so far, NAC activity has only been confirmed for HIV-1 and RSV Gag polyproteins. The nucleocapsid (NC) domain of Gag is proposed to be crucial for interactions with nucleic acids and NAC activity. The major function of matrix (MA) domain is targeting and binding of Gag to the plasma membrane but MA can also interact with RNA and influence NAC activity of Gag. Here, we characterize RNA binding properties and NAC activity of HIV-2 MA and Gag, lacking p6 domain (GagΔp6) and discuss potential contribution of NC and MA domains to HIV-2 GagΔp6 functions and interactions with RNA. RESULTS: We found that HIV-2 GagΔp6 is a robust nucleic acid chaperone. HIV-2 MA protein promotes nucleic acids aggregation and tRNA(Lys3) annealing in vitro. The NAC activity of HIV-2 NC is affected by salt which is in contrast to HIV-2 GagΔp6 and MA. At a physiological NaCl concentration the tRNA(Lys3) annealing activity of HIV-2 GagΔp6 or MA is higher than HIV-2 NC. The HIV-2 NC and GagΔp6 show strong binding to the packaging signal (Ψ) of HIV-2 RNA and preference for the purine-rich sequences, while MA protein binds mainly to G residues without favouring Ψ RNA. Moreover, HIV-2 GagΔp6 and NC promote HIV-2 RNA dimerization while our data do not support MA domain participation in this process in vitro. CONCLUSIONS: We present that contrary to HIV-1 MA, HIV-2 MA displays NAC activity and we propose that MA domain may enhance the activity of HIV-2 GagΔp6. The role of the MA domain in the NAC activity of Gag may differ significantly between HIV-1 and HIV-2. The HIV-2 NC and MA interactions with RNA are not equivalent. Even though both NC and MA can facilitate tRNA(Lys3) annealing, MA does not participate in RNA dimerization in vitro. Our data on HIV-2 indicate that the role of the MA domain in the NAC activity of Gag differs not only between, but also within, retroviral genera.