Ludmila Perelygina

• Ph.D.
• Senior Researcher at Centers for Disease Control and Prevention

Background There is a known association between common variable immunodeficiency (CVID) and granulomas in multiple organ systems, including the skin, lung, liver, and spleen. Rubella virus has also been detected within cutaneous granulomas in both immunocompetent and immunocompromised hosts. We present a retrospective case series of patients with C...

Measles and rubella are vaccine-preventable viral diseases and can be prevented by safe, highly effective vaccination with measles- and rubella-containing vaccines. Given the myriad causes of febrile exanthems, laboratory surveillance for both measles and rubella is important to document the incidence of these diseases and to track the progress and...

The association between granulomas and vaccine-derived rubella virus (VDRV) in people with primary immunodeficiencies has raised concerns about the ability of immunoglobulin preparations to neutralize VDRVs. We investigated the capacity of immunoglobulin to neutralize rubella vaccine virus and 4 VDRV strains. As expected, the rubella vaccine virus...

Infectious susceptibility is a component of many inborn errors of immunity. Nevertheless, antibiotic use is often used as a surrogate in history taking for infectious susceptibility, thereby disadvantaging patients who present with viral infections as their phenotype. Further complicating clinical evaluations are unusual manifestations of viral inf...

Patients with inborn errors of immunity (IEI) may develop granulomas in multiple organ systems including the skin. Vaccine strain rubella virus (RuV), part of the live attenuated measles, mumps, and rubella (MMR) vaccine, has been identified within these granulomas. RuV is typically found in macrophages; however, recently neutrophils have been iden...

Measles virus is the prototypic member of the genus Morbillivirus in the family Paramyxoviridae , and it is the only member of the genus that causes human disease. Characteristic cytopathic effects of measles virus infection include giant multinucleated cells (Warthin‐Finkeldey giant cells) as well as intracytoplasmic and intranuclear cellular incl...

Measles virus is the prototypic member of the genus Morbillivirus in the family Paramyxoviridae , and it is the only member of the genus that causes human disease. Characteristic cytopathic effects of measles virus infection include giant multinucleated cells (Warthin‐Finkeldey giant cells) as well as intracytoplasmic and intranuclear cellular incl...

Rubella is a highly contagious viral infection that usually causes a mild disease in children and adults. However, infection during pregnancy can result in a fetal or newborn death or congenital rubella syndrome (CRS), a constellation of permanent birth defects including cataracts, heart defects, and sensorineural deafness. The live-attenuated rube...

Since the initial identification of vaccine-derived rubella virus (RuV) in the cutaneous granulomas of pediatric patients with inborn errors of immunity (IEI) in 2014, more than 80 cases of RuV granulomas have been reported implicating both vaccine-derived and wild type RuV. Previously thought to arise exclusively in patients with significant immun...

We present a case of cutaneous granulomatous disease associated with rubella virus in a 4-year-old girl without an identifiable immunodeficiency. In this case, a combination of anti-inflammatory, anti-viral, and anti-neutrophil therapies successfully treated vision-threatening eyelid, conjunctival, scleral, and orbital inflammation.

A young man with X-linked severe combined immunodeficiency developed a persistent vaccine-derived rubella virus (VDRV) infection, with the emergence of cutaneous granulomas more than fifteen years after receipt of two doses of measles-mumps-rubella (MMR) vaccine. Following nasopharyngeal swab (NP) collection, VDRV was detected by real-time polymera...

We report two patients with DNA repair disorders (Artemis deficiency, Ataxia telangiectasia) with destructive skin granulomas, presumably triggered by live-attenuated rubella vaccinations. Both patients showed reduced naïve T cells. Rapid resolution of skin lesions was observed following hematopoietic stem cell transplantation. However, the patient...

An examination of the nucleic acid sequence alignment of 48 full-length rubella virus genomes revealed that the 5’ terminus of the genome is more conserved than the commonly used detection windows for rubella virus RNA located in the E1 protein coding region, suggesting that the 5’ terminus could be a target for improving detection of all rubella v...

Importance: Vaccine-derived and wild-type rubella virus (RuV) has been identified within granulomas in patients with inborn errors of immunity, but has not been described in granulomas of healthy adults. Objective: To determine the association between RuV and atypical granulomatous inflammation in immune-competent adults. Design, setting, and p...

A strong association between rubella virus (RuV) and chronic granulomas, in individuals with inborn errors of immunity, has been recently established. Both the RA27/3 vaccine and wild-type RuV strains were highly sensitive to a broad-spectrum antiviral drug, nitazoxanide (NTZ), in vitro. However, NTZ treatment, used as a salvage therapy, resulted i...

Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, vi...

Importance Immunodeficiency-related, vaccine-derived rubella virus (RuV) as an antigenic trigger of cutaneous and visceral granulomas is a rare, recently described phenomenon in children and young adults treated with immunosuppressant agents. Objective To perform a comprehensive clinical, histologic, immunologic, molecular, and genomic evaluation...

Purpose of the review: The aim of this article is to summarize recent data on rubella virus (RuV) vaccine in chronic inflammation focusing on granulomas in individuals with primary immunodeficiencies (PIDs). Recent findings: The live attenuated RuV vaccine has been recently associated with cutaneous and visceral granulomas in children with vario...

Rubella viruses (RV) have been found in an association with granulomas in children with primary immune deficiencies (PID). Here, we report the recovery and characterization of infectious immunodeficiency-related vaccine-derived rubella viruses (iVDRV) from diagnostic skin biopsies of four patients. Sequence evolution within PID hosts was studied by...

Granulomatous disease prompts a search for antigenic triggers, given our understanding of granuloma formation as a defense mechanism against persistent antigen in tissue. Cutaneous granulomas in patients with primary immunodeficiency have been attributed to immune dysregulation because no infectious trigger has been identified in these patients.¹ H...

The association of immunodeficiency-related vaccine-derived rubella virus (iVDRV) with cutaneous and visceral granulomatous disease has been reported in patients with primary immunodeficiency disorders (PIDs). The majority of these PID patients with rubella-positive granulomas had DNA repair disorders. To support this line of inquiry, we provide ad...

Purpose Nitazoxanide was recently reported as having in vitro effectiveness against the rubella virus. Immunodeficiency-related vaccine-derived rubella occurs in some patients who have an inherited immunodeficiency and who received the MMR vaccine. This study investigated the in vivo effectiveness of nitazoxanide therapy. Methods This is a retrosp...

Purpose: Granulomas are a potentially severe condition that can last for several years in persons with primary immunodeficiency disorders (PIDD). We assessed the prevalence of granulomas in patients with PIDD. Methods: We used the Truven Health MarketScan® 2005-2015 Commercial Claims and Encounters and 2006-2015 Medicaid databases and the US Imm...

In summary, the patient developed a mild hemiparesis and slurred speech before interferon-α treatment. During peginterferon-alfa-2a therapy, a slow progression in her neurological symptoms was observed. A similar interfer- on treatment attempt against JCV PML was also ineffec- tive in a previously reported PID case [1]. However, it seems likely tha...

Persistent rubella virus (RV) infection has been associated with various pathologies such as congenital rubella syndrome, Fuchs's uveitis, and cutaneous granulomas in patients with primary immune deficiencies (PID). Currently there are no drugs to treat RV infections. Nitazoxanide (NTZ) is an FDA-approved drug for parasitic infections, and has been...

Importance: B virus causes brainstem destruction in zoonotically infected humans in the absence of timely diagnosis and intervention. Nectins are cell adhesion molecules that are widely expressed in human tissues, including neurons and neuronal synapses. Here we report that human nectin-2 is a target receptor for B virus entry in addition to repor...

Background Rubella virus (RV) infection is usually a mild illness in children and adults. However, maternal infection during the first trimester of pregnancy can lead to congenital rubella syndrome (CRS) in the infant. Fetuses with CRS show damage to the endothelium of the heart and blood vessels; thus, it has been speculated that the clinical mani...

Background: An estimated 100,000 cases of congenital rubella syndrome (CRS) occur worldwide each year. The reported mortality rate for infants with CRS is up to 33%. The cellular mechanisms responsible for the multiple congenital defects in CRS are presently unknown. Here we identify cell types positive for rubella virus (RV) in CRS infants. Method...

Both wild type (WT) and vaccine rubella virus (RV) can pass through the placenta to infect a human fetus, but only wtRV routinely causes pathology. To investigate possible reasons for this, we compared establishment of persistence of wtRV and RA27/3 vaccine strains in fetal endothelial cells. We showed that yields of RA27/3 and wtRV were similar af...

Unlabelled: Glycoprotein D (gD) plays an essential role in cell entry of many simplexviruses. B virus (Macacine herpesvirus 1) is closely related to herpes simplex virus 1 (HSV-1) and encodes gD, which shares more than 70% amino acid similarity with HSV-1 gD. Previously, we have demonstrated that B virus gD polyclonal antibodies were unable to neu...

Cardiovascular abnormalities are the leading cause of neonatal death among patients with congenital rubella syndrome (CRS). Although persistence of rubella virus (RV) in fetal endothelium has been repeatedly suggested as a possible cause of cardiovascular birth defects, evidence of the permissiveness of fetal endothelial cells to RV is lacking. In...

B virus (Macacine herpesvirus 1) occurs naturally in macaques and can cause lethal zoonotic infections in humans. Detection of B virus (BV) antibodies in macaques is essential for the development of SPF breeding colonies and for diagnosing infection in macaques that are involved in human exposures. Traditionally, BV infections are monitored for pre...

A 6.5-year-old female eastern black and white colobus monkey (Colobus guereza) was evaluated after acute onset of ataxia and inappetence. The monkey was ataxic and lethargic, but no other abnormalities were detected via physical examination, radiography, or clinicopathologic analyses. During the next 2 days, the monkey's clinical condition deterior...

B virus (cercopithecine herpesvirus 1) is the only deadly alphaherpesvirus that is zoonotically transmissible from macaques to humans. The detection of humoral immune responses is the method of choice for the rapid identification of B virus-infected animals. We evaluated the diagnostic potential of recombinant B virus glycoproteins for the detectio...

As the human genome project progresses and some microbial and eukaryotic genomes are recognized, a novel technology, DNA microarray (also called gene chip, biochip, gene microarray, and DNA chip) technology, has attracted increasing number of biologists, bioengineers and computer scientists recently. This technology promises to monitor the whole ge...

The timing of T-cell infiltration of the hypothalamus is crucial in the prevention of bilateral retinitis in mice inoculated with HSV-1 through the anterior chamber (AC). In H129-infected mice, T-cells are recruited to the suprachiasmatic nuclei of the hypothalamus too late to protect infected mice from development of bilateral retinitis. The purpo...

The complete DNA sequence of herpes B virus (Cercopithecine herpesvirus 1) strain E2490, isolated from a rhesus macaque, was determined. The total genome length is 156,789 bp, with 74.5% G+C composition and overall genome organization characteristic of alphaherpesviruses. The first and last residues of the genome were defined by sequencing the clon...

A TaqMan based real-time PCR assay was developed for rapid detection and quantitation of herpes B virus (Cercopithecine herpesvirus 1) in clinical samples. The assay utilizes B virus-specific primers and a probe to the non-conserved region of the gG gene to discriminate B virus from closely related alphaherpesviruses. Fifty copies of B virus DNA co...

Genes encoding glycoproteins gB, gC, gD, gE, and gG of herpes B virus (species Cercopithecine herpesvirus 1) were cloned into mammalian expression vector pcDNA3.1/V5-His. Abilities of the plasmid constructs to express recombinant glycoproteins were confirmed by Western blot analysis of transfected CHO-K1 and COS-7 cells. Antibody production was ind...

The mapping of linear epitopes of B virus (Cercopithecine herpesvirus 1 and herpes B virus) glycoprotein D (gD) was accomplished by screening the constructed gD epitope library with serum from B virus–infected macaques. The immunodominant epitope, gD (362–370), was identified within the C-terminal region of B virus gD that was highly conserved amon...

The GAGA factor (GAF) of Drosophila melanogaster encoded by the Trithorax-like gene is known to maintain expression of many Drosophila genes including homeotic ones, through configuration remodeling of local chromatin. The complicated transcript pattern of the GAF gene has been revealed at all stages of development. The study of GAF gene expression...

A 323-bp DNA fragment (U15557) was isolated, cloned, and sequenced after polymerase chain reaction (PCR) amplification from Monodelphis domestica genomic DNA. A HindIII restriction fragment length polymorphism was identified in this species using the U15557 PCR, fragment as a hybridization probe. DNA samples exhibited either a 6.4 kb band, a 7.2 kb...

On May 13, 1994 this sequence version replaced gi:8283.

A cDNA copy of the Nc70F gene which is specifically expressed in Drosophila neural tissue was cloned and characterized. The gene has an open reading frame for the protein of 384 amino acids. The protein contains dimerization, DNA binding, activation and repression domains which are common for the eucaryotic transcription factors. However, the domai...

Molecular-genetic analysis of the Nc (neural conserved) genome sequence of Drosophila melanogaster located at the position 73EF of Drosophila melanogaster was performed. The Nc73EF sequence was shown to be expressed in the nervous system of Drosophila. We constructed the restriction map of this sequence and revealed the main RNA-coding fragment in...

Nuclear protein which selectively binds to the Alu-family DNA repeat (AFR, Blur8) is partially purified from human HeLa cells using a gel retention assay. At low protein concentrations only a single complex of the protein with AFR is formed (CII). Increasing protein concentrations lead to the gradual disappearance of CII, being replaced by complexe...

In nuclear extract of HeLa cells two proteins were identified having the specific binding activity to cloned 1.8kb fragment of human satellite DNA III (HS3). One of the satellite binding proteins (SBP1) purified by column chromatography using DEAE-, phospho- and DNA-cellulose steps interacted also with adenovirus 5 replication enhancer (ARE), anoth...

Two proteins with molecular weights of 40 and 80 kDa which are able to bind human Alu-repeat in a sequence-specific manner were found in HeLa nuclear extracts. The proteins were partially purified by column chromatography on DEAE-cellulose, phosphocellulose and FPLC MonoQ sorbent. One of the Alu-binding proteins (ABP2 with m. w. of 80 kDa) was foun...

Using a gel retardation assay the protein which binds selectively to the Alu-family repeat (AFR) has been identified and partially purified from HeLa cell nuclear extract. The protein (AFR-binding protein, ABP) forms multiple discrete complexes with AFR even in the presence of 200 to 2000-fold excess of non-specific (E. coli) DNA. The most stable c...

Nuclear proteins from HeLa cells specifically binding to the Alu-repeat cloned in the plasmid Blur8 have been studied. 0.35 M nuclear extract proteins have been separated on DEAE-cellulose. The presence of DNA-binding proteins has been found in all fractions by the technique of DNA-binding on nitrocellulose filters. The labelled restricted DNA of t...