Intranuclear Viral Particles Research Articles

Eptesipox virus-associated lesions in naturally infected big brown bats.

Bats have many unique qualities amongst mammals; one of particular importance is their reported tolerance to viruses without developing disease. Here, the authors present evidence to the contrary by describing and demonstrating viral nucleic acids within lesions from eptesipox virus (EfPV) infection in big brown bats. One hundred and thirty bats submitted for necropsy from Saskatchewan, Canada, between 2017 and 2021 were screened for EfPV by polymerase chain reaction (PCR); 2 had amplifiable poxvirus DNA. The lesions associated with infection were oral and pharyngeal ulcerations and joint swelling in 2/2 and 1/2 cases, respectively. These changes were nonspecific for poxvirus infection, although intracytoplasmic viral inclusion bodies within the epithelium, as observed in 2/2 bats, are diagnostic when present. Viral nucleic acids, detected by in situ hybridization (ISH), were observed in the epithelium adjacent to ulcerative lesions from both cases and within the joint proliferation of 1 case. A new isolate of EfPV was obtained from 1 case and its identity was confirmed with electron microscopy and whole genome sequencing. Juxtanuclear replication factories were observed in most cells; however, rare intranuclear virus particles were also observed. The significance of the presence of virus particles within the nucleus is uncertain. Whole genome assembly indicated that the nucleotide sequence of the genome of this EfPV isolate was 99.7% identical to a previous isolate from big brown bats in Washington, USA between 2009 and 2011. This work demonstrates that bats are not resistant to the development of disease with viral infections and raises questions about the dogma of poxvirus intracytoplasmic replication.

Diagnosis and phylogenetic analysis of bovine papillomaviruses in cattle papillomatosis cases by different methods

Papillomaviruses, known as epitheliotropic, cause proliferation in the skin, mucosa, and different visceral organs. In this study, it was aimed to diagnose bovine papillomavirus (BPV) by using different methods in the lesion taken from twenty cattle with papillomas in different areas of the body and to reveal its molecular characterization. In our study, molecular, immunohistochemistry, and transmission electron microscopy (TEM) methods were used for virus identification. Additionally, sequencing analysis was used to ascertain the phylogenetic relationship between the obtained field strains and other isolates submitted to GenBank. Histopathological analyses of the collected samples were done in addition to diagnostic procedures. Intranuclear virus particles were detected when the papillomas were investigated with TEM. In PCR analyses using degenerate and type-specific primer sets, the presence of BPV nucleic acid was determined in 70% (14/20) and 90% (18/20) of the samples, respectively. No virus could be detected in PCR applications using MY 09/11 degenerate primer sets. Twenty animals of different ages, races, and genders included in the study by random sampling method from different herds were divided into 4 groups according to the body regions where the lesions were located. Sequence analysis was performed on a sample from each group that showed strong positivity in the PCR technique using FAP 59/64 degenerate primer set and type-specific primer set. Sequence analyses were performed using FAP 59/64 degenerate primers of amplicons for phylogenetic research. In these analyses, three of the isolated strains were identified as BPV-1, which is in the Deltapapillomavirus 4 genus, and one as BPV-2. As a result of the study, it was concluded that molecular and phylogenetic studies using type-specific primers are more beneficial in order to fully reveal the etiology of papillomatosis in cattle and it would be correct to determine BPV types before prophylactic (vaccine, etc.) applications.

Phylogenetic analysis and searching bovine papillomaviruses in teat papillomatosis cases in cattle by performing histopathology, immunohistochemistry, and transmission electron microscopy.

Papillomaviruses are epitheliotropic in nature and cause proliferation in the skin, mucosa, and various internal organs of various animal species. The lesions they cause, specifically in cattle teats, lead to significant economic losses in the milk industry. In this study, we identified the bovine papillomaviruses (BPVs) responsible for teat papillomas in cattle. The tissue damage caused by the virus was examined histopathologically using immunohistochemical, transmission electron microscopy (TEM), and molecular methods. Additionally, sequence analyses were performed on the isolated field strains to better understand their genetic and phylogenetic relationships with previously reported isolates. Teat papillomatosis was confirmed in the collected samples by histopathological and immunohistochemical methods, which were followed by other diagnostic methods. Intranuclear virus particles were found in the epithelial cells during a TEM examination of teat lesions. BPV was detected in seven samples by performing PCR using degenerate primers and specific primers. The positive samples were used for typing through sequence analysis/PCR with type-specific primers. Three isolates from teat tissues with BPV infection were identified as BPV-6, two as BPV-10, one as BPV-2, and one as BPV-8. The five isolates identified through sequence analysis of positive samples belonged to the Xipapillomavirus 1 genus (one), the Epsilonpapillomavirus 1 genus (one), and the Deltapapillomavirus genus (one) (three). Furthermore, type-specific primers were found to be useful for molecular diagnosis of BPV, which occurs in the etiology of teat papillomas, followed by genotyping and primer generation during characterization. The detection of BPV types and their prevalence, biosafety measures in animal breeding, and the importance of vaccine research are all important.

Cheilitis Associated with a Novel Herpesvirus in Two Panther Chameleons (Furcifer pardalis)

Intracellular epidermal inclusions were detected within histological sections of skin biopsies from two panther chameleons (Furcifer pardalis) with chronic cheilitis. Transmission electron microscopy (TEM) confirmed the abundant presence of icosahedral intracytoplasmic and intranuclear viral particles in infected keratinocytes, with an average diameter of 120-125nm, consistent with herpesviruses (HVs). TEM also revealed the presence of virions in intercellular spaces and keratinocyte nuclei and features suggestive of capsid assembly, nuclear egress with primary envelopment and anterograde transport leading to virion assembly and release. Polymerase chain reaction (PCR) primers targeting a conserved region of herpesvirus DNA-dependent DNA polymerase were used to amplify and sequence a product from a nested HV PCR performed on skin biopsies of both chameleons. Comparative sequence analysis indicates that the virus detected in both chameleons was a novel member of the Alphaherpesvirinae, which we refer to as chamaeleonid herpesvirus 1 (chamHV 1). Based on the identical findings in both chameleons, we consider chamHV 1 to be a candidate aetiological agent of cheilitis in panther chameleons. This is the first report of skin lesions in a chameleon species associated with HV infection.

Virus-like particles and enterovirus antigen found in the brainstem neurons of Parkinson’s disease

Background: In a previous study on encephalitis lethargica, we identified a virus related to enterovirus in autopsy brain material. Transmission electron microscopy (TEM), immunohistochemistry (IHC) and molecular analysis were employed. Our present objective was to investigate, using a similar approach, as to whether virus-like particles (VLP) and enterovirus antigen are present in Parkinson’s disease (PD) brainstem neurons. Methods: Fixed tissue from autopsy specimens of late onset PD and control brainstem tissue were received for study. The brain tissue was processed for TEM and IHC according to previous published methods. Results: We observed VLP in the brainstem neurons of all the cases of PD that were examined. In the neurons’ cytoplasm there were many virus factories consisting of VLP and endoplasmic reticulum membranes. In some neurons, the virus factories contained incomplete VLP. Complete VLP in some neurons’ virus factories had an average diameter of 31 nm, larger than control brain ribosomes. In the nuclei, there were VLP with an average diameter of 40 nm. In cases of human poliomyelitis, there were cytoplasmic virus factories and intranuclear virus particles similar to those observed in PD. On preparing PD brain sections for IHC there was positive staining using anti-poliovirus antibody and anti-coxsackie antibody. This result was statistically significant. Conclusions: We present evidence for an enterovirus infection in PD. For future studies, virus isolation and molecular analysis are suggested.

Virus-like particles and enterovirus antigen found in the brainstem neurons of Parkinson’s disease

Background: In a previous study on encephalitis lethargica, we identified a virus related to enterovirus in autopsy brain material. Transmission electron microscopy (TEM), immunohistochemistry (IHC) and molecular analysis were employed. Our present objective was to investigate, using a similar approach, as to whether virus-like particles (VLP) and enterovirus antigen are present in Parkinson’s disease (PD) brainstem neurons. Methods: Fixed tissue from autopsy specimens of late onset PD and control brainstem tissue were received for study. The brain tissue was processed for TEM and IHC according to previous published methods. Results: We observed VLP in the brainstem neurons of all the cases of PD that were examined. In the neurons’ cytoplasm there were many virus factories consisting of VLP and endoplasmic reticulum membranes. In some neurons, the virus factories contained incomplete VLP. Complete VLP in some neurons’ virus factories had an average diameter of 31 nm, larger than control brain ribosomes. In the nuclei, there were VLP with an average diameter of 40 nm. In cases of human poliomyelitis, there were cytoplasmic virus factories and intranuclear virus particles similar to those observed in PD. On preparing PD brain sections for IHC there was positive staining using anti-poliovirus antibody and anti-coxsackie antibody. This result was statistically significant. Conclusions: We present evidence for an enterovirus infection in PD. For future studies, virus isolation and molecular analysis are suggested.

Virus-like particles and enterovirus antigen found in the brainstem neurons of Parkinson's disease.

Background: In a previous study on encephalitis lethargica, we identified an enterovirus in autopsy brain material. Transmission electron microscopy (TEM), immunohistochemistry (IHC) and molecular analysis were employed. Our present objective was to investigate, using a similar approach, as to whether virus-like particles (VLP) and enterovirus antigen are present in Parkinson's disease (PD) brainstem neurons. Methods: Fixed tissue from autopsy specimens of late onset PD and control brainstem tissue were received for study. The brain tissue was processed for TEM and IHC according to previous published methods. Results: We observed VLP in the brainstem neurons of all the cases of PD that were examined. In the neurons' cytoplasm there were many virus factories consisting of VLP and endoplasmic reticulum membranes. In some neurons, the virus factories contained incomplete VLP. Complete VLP in some neurons' virus factories had an average diameter of 31 nm, larger than control brain ribosomes. In the nuclei, there were VLP with an average diameter of 40 nm. In cases of human poliomyelitis, there were cytoplasmic virus factories and intranuclear virus particles similar to those observed in PD. On preparing PD brain sections for IHC there was positive staining using anti-poliovirus antibody and anti-coxsackie antibody. This result was statistically significant. Conclusions: We present evidence for an enterovirus infection in PD. For future studies, virus isolation and molecular analysis is suggested.

Virus-associated papillomatous skin lesions in a giant guitarfish Rhynchobatus djiddensis: a case report.

Although elasmobranch species are increasingly displayed in public aquaria, knowledge of disease in wild and captive elasmobranchs, as well as the agents involved, remains limited, and descriptions are often incomplete. This report describes papillomatous skin lesions in a juvenile giant guitarfish Rhynchobatus djiddensis associated with intranuclear viral particles. Skin biopsies were collected from multiple, friable, raised, villonodular skin lesions affecting pigmented and non-pigmented skin of the caudal fin and ventrum, respectively. Microscopic examination revealed papillary proliferation of the epidermis, with widespread marked karyomegaly of squamous epithelial cells. In approximately 75% of nuclei, chromatin was marginated by one to multiple, large, amphophilic inclusions. Large numbers of unencapsulated, 75 nm, icosahedral viral particles were observed to form large arrays in affected nuclei using transmission electron microscopy. Based on intranuclear location, particle size and morphology, a consensus nested-PCR for adenovirus polymerase was attempted. However, no adenoviral gene sequence was amplified. The nature of the involved virus remains unknown and an ongoing area of investigation. Lesions regressed completely over a 6 mo period, during which time the animal showed no signs of systemic illness, and there has been no recrudescence for 6 mo following resolution. Two cohorts of similar age and in close contact with the case animal were unaffected.

Primary gastric Merkel cell carcinoma harboring DNA polyomavirus

Merkel cell carcinoma (MCC) is a skin cancer that can also rarely arise in extracutaneous sites including mucosal surfaces. About 80% of MCCs harbor the Merkel cell polyomavirus (MCPyV). All cases of gastric MCCs so far reported were metastases from cutaneous sources. In the present article, we describe for the first time a primary gastric MCC harboring MCPyV. A 72-year-old man presented to clinical observation due to epigastric pain. Upper endoscopy revealed an ulcerated gastric tumor. The patient underwent total gastrectomy. The tumor was composed of mitotically active monomorphic small cells showing round nuclei with finely dispersed chromatin arranged in sheets and nests with large areas of necrosis. Tumor cells were positive for neuroendocrine markers and showed paranuclear dot immunoreactivity for cytokeratin 20. MCPyV was demonstrated with immunohistochemistry and electron microscopy, which showed intranuclear and intracytoplasmic viral particles. The MCPyV DNA in tumor cells was demonstrated with polymerase chain reaction analysis.

Lethal Herpesvirosis in 16 Captive Horned Vipers (Vipera ammodytes ammodytes): Pathological and Ultrastructural Findings

Sixteen captive adult horned vipers (Vipera ammodytes ammodytes) were submitted for necropsy examination following a 2-week history of lethargy, anorexia and dyspnoea. Gross lesions included widespread haemorrhage, serosanguineous effusions in the body cavities and multiple pinpoint white to yellow foci in the liver. Microscopically, there was multifocal hepatic coagulative necrosis associated with intranuclear acidophilic inclusion bodies in sinusoidal endothelial cells. Similar endothelial lesions were observed in the myocardium, fat bodies, kidneys and spleen. Transmission electron microscopy revealed numerous virions (100-110 nm) in the nuclei of endothelial cells and intracytoplasmic enveloped virions (140-150 nm) were also found. The gross and histological findings and the ultrastructural features of the intranuclear inclusions and viral particles were consistent with herpesviral infection. To the best of our knowledge, these are the first reported cases of a lethal herpesvirosis in horned vipers and the second report in snakes.

A novel herpesvirus associated with respiratory disease in Bourke's parrots (Neopsephotus bourkii)

A novel herpesvirus infection in nine Bourke's parrots (Neopsephotus bourkii, formerly Neophema bourkii) housed in an outdoor aviary comprised of multiple species of birds was diagnosed based on histopathology, electron microscopy and polymerase chain reaction (PCR). Clinical signs in the parrots included anorexia, ruffled feathers, depression, loss of weight and respiratory distress. The most common gross lesions were moderately congested and oedematous lungs and a mild fibrinous exudate in the air sacs and lumen of the trachea. Histological examination revealed mild to severe bronchopneumonia and airsacculitis with syncytial cells containing eosinophilic intranuclear inclusion bodies in most birds. Other less frequent changes included tracheitis, syringitis, sinusitis, rhinitis, otitis media and conjunctivitis. Attempts to culture the virus in chicken embryos and chicken embryo liver cells were unsuccessful. Examination by transmission electron microscopy of syncytial cells from the lungs of two birds revealed intranuclear virus particles typical of the family Herpesviridae. DNA from a novel herpesvirus was amplified from lung tissue by PCR using degenerate primers derived from conserved avian herpesvirus sequences. The virus belongs in the genus Iltovirus of the Alphaherpesvirinae subfamily. It is not closely related to Psittacid herpesvirus 1 that causes Pacheco's disease but does group phylogenetically with a clade of herpesviruses that cause respiratory disease in a number of avian species. The proposed name for this herpesvirus is Psittacid herpesvirus 3.

Molecular diagnosis of a laboratory mouse papillomavirus (MusPV)

MusPV, a novel papillomavirus (PV) that naturally infects laboratory mice, was isolated and characterized from a colony of NMRI-Foxn1nu/Foxn1nu (nude) mice in India. Because MusPV may have been missed during routine pathogen screening of mice in colonies worldwide, a variety of detection methods are described to detect MusPV. The clinical and histologic lesions of productive MusPV infections fit PV-associated features, including papillomas, koilocytes within the stratum granulosum of the hyperplastic/acanthotic papillomatous epithelium, and the presence of intranuclear virus particles in koilocytotic cells visualized by electron microscopy. Antiserum against disrupted PV virions, isolated from another species (canine), identified conserved viral antigens in productively infected cells by immunohistochemistry. A rolling circle technique was used to amplify viral circular DNAs followed by endonuclease restriction enzyme digestion to determine the correct size of PV DNA. Consensus PV degenerative primers, My09/11, commonly used to detect many different types of PVs by polymerase chain reaction (PCR), particularly mucosotropic HPVs, also identified MusPV and all rodent PVs tested. Since there was one nucleotide mismatch between the My09/11 primer set and the MusPV template, a new primer set, MusPV–My09/11, was designed to specifically detect MusPV in latent infections and spontaneous MusPV-induced papillomas. Southern blot analysis verified the presence of full size PV DNA in infected tissues. Virus-like particles (VLPs), generated from MusPV L1 genes, provided a substrate for serological testing of naturally and experimentally infected mice. In summary, a series of diagnostic assays were developed and validated to detect MusPV infection in skin tumors and serological response in laboratory mice.

Evidence for an enterovirus as the cause of encephalitis lethargica.

BackgroundThe epidemic of encephalitis lethargica (EL), called classical EL, was rampant throughout the world during 1917–1926, affecting half a million persons. The acute phase was lethal for many victims. Post-encephalitic parkinsonism (PEP) affected patients for decades. Our purpose was to investigate the cause of classical EL by studying the few available brain specimens. Cases of PEP and modern EL were also studied. Transmission electron microscopy (TEM) and immunohistochemistry were employed to examine brain from four classical EL cases, two modern EL cases and one PEP case.MethodsStandard methods for TEM, immunohistochemistry and RTPCR were applied.Results27 nm virus-like particles (VLP) were observed in the cytoplasm and nuclei of midbrain neurons in all classical EL cases studied. Large (50 nm) VLP and 27 nm intranuclear VLP were observed in the modern EL cases and the PEP case. Influenza virus particles were not found. VLP were not observed in the control cases. TEM of cell cultures inoculated with coxsackievirus B4 and poliovirus revealed both small and large intranuclear virus particles and small cytoplasmic particles, similar to the VLP in EL neurons. In the EL brains, nascent VLP were embedded in putative virus factories and on endoplasmic reticulum (ER). The VLP in the cases of classical EL survived, whereas ribosomes underwent autolysis due to the lack of refrigeration and slow formaldehyde fixation of whole brain. The VLP were larger than ribosomes from well preserved brain. Immunohistochemistry of classical EL cases using anti-poliovirus and anti-coxsackievirus B polyclonal antibodies showed significant staining of cytoplasm and nuclei of neurons as well as microglia and neuropil. Purkinje cells were strongly stained.A 97-bp RNA fragment of a unique virus was isolated from brain tissue from acute EL case #91558. Sequence analysis revealed up to 95% identity to multiple human Enteroviruses. Additional cases had Enterovirus positive reactions by real time PCR.ConclusionsThe data presented here support the hypothesis that the VLP observed in EL tissue is an Enterovirus.

Feline Epidermal Nevi Resembling Human Inflammatory Linear Verrucous Epidermal Nevus

Multiple, pigmented, verrucous, cutaneous lesions in a 2-year-old female cat were pathologically examined. The lesions were linearly arranged on the right side of the body, and had developed along with moderate pruritus since infancy. Histologically, prominent exophytic, papillomatous outgrowths of the epidermis and acanthosis with intense ortho and parakeratotic hyperkeratosis were characteristic of the lesions. Dermal inflammation with mononuclear cells, neutrophils, and eosinophils was also noted. Inclusion bodies, cellular degeneration, and intranuclear viral particles suggesting papillomavirus infection in the keratinocytes were not observed. Papillomavirus antigen and DNA were not detected in the lesions by immunohistochemistry and polymerase chain reaction, respectively. In accordance with these clinical and histopathological features, the cutaneous lesions of the present cat were diagnosed as epidermal nevi, which were consistent with human inflammatory linear verrucous epidermal nevi.

Trichodysplasia of immunosuppression treated with oral valganciclovir

Trichodysplasia of immunosuppression (TOI) is a newly described rare clinicopathologic entity usually found in transplant patients on chronic immunosuppressive medications or with hematologic malignancies. TOI consists of a cutaneous eruption of spiny papules predominantly affecting the face and arms. The distinct histopathologic picture includes abnormally maturing anagen follicles with hyperkeratotic infundibula and excessive inner root sheath differentiation. Given that intranuclear viral particles have been noted on electron microscopy of skin biopsy in several patients, a viral etiology is suspected. These viral particles are similar in shape and size to a polyoma virus, however, the virus has not been identified to date. There are reports of improvement of TOI with topical cidofovir or tazarotene 0.5% gel, but to our knowledge there has not been a report of near-complete resolution with oral valganciclovir. We report a case of TOI in a heart transplant patient on a chronic immunosuppressive regimen of sirolimus, mycophenolic acid and prednisone that demonstrated almost complete response to treatment with systemic valganciclovir.

Viral‐associated trichodysplasia in a patient with lymphoma: a case report and review

Viral-associated trichodysplasia is a recently described entity associated with immunosuppression. We describe a 68-year-old man with a history of treated lymphoma who developed numerous, disfiguring, papular and spiny lesions involving most of the central face. Both facial and body alopecia was noted. Histopathologic findings of a facial papule showed dramatic alterations of the hair bulbs, including bulbar distention, lack of hair shaft formation and a marked expansion of inner root sheath type epithelium. These findings were identical to those of previously described cases, so electron microscopy was performed. Numerous intranuclear virus particles were identified. Shortly after the diagnosis of trichodysplasia was made, the patient was found to have a relapse of his lymphoma, which may represent the source of his immunosuppression. Based on his skin biopsy findings, successful antiviral therapy was initiated. This case and a review of previously reported cases are discussed in this study.

Equine Herpesvirus 2-Associated Granulomatous Dermatitis in a Horse

Granulomatous dermatitis in horses has been linked to many etiologies, including various parasites, fungi, and bacteria. Idiopathic forms of granulomatous inflammation-producing diseases, some of which are localized to the skin, also have been reported in horses. Herein we describe a case of recurrent equine granulomatous skin disease characterized by intranuclear viral inclusions within macrophages and giant cells. The histologic changes were primarily noted in the deep dermis and included multifocal to coalescing areas of necrosis marked by histiocytic cell infiltration and presence of giant cells. Electron microscopic examination revealed intranuclear and intracytoplasmic viral particles consistent with herpesvirus. Sequence results of the polymerase chain reaction product were consistent with equine herpesvirus 2, adding another possible etiology to the list of differentials in cases of equine granulomatous skin disease.

Virus-Associated Trichodysplasia Spinulosa

Virus-associated trichodysplasia spinulosa (VATS) is a cutaneous eruption of spiny papules predominantly affecting the face that is associated with a distinctive histologic picture of abnormally maturing anagen follicles with excessive inner root sheath differentiation and hyperkeratotic infundibula. Ultrastructurally, intranuclear viral particles consistent with polyoma virus are found. Only 2 patients have thus far been reported. Both had developed the eruption after a kidney transplant. We report 2 additional cases of VATS. One is an 8-year-old boy who presented with facial papules after a kidney transplant. The other is a 19-year-old man with a history of acute lymphocytic leukemia who never had a transplant. He developed a papular facial eruption as well as alopecia. Light microscopic and ultrastructural examinations revealed a spectrum in the severity of the histologic alterations as well as the number of intranuclear viral particles. This report expands the range of pathologic alterations associated with VATS and documents for the first time that it can affect patients without a solid organ transplant. The similarity of the clinical and histologic features of VATS with those previously reported by others as cyclosporine-induced "follicular dystrophy" or "pilomatrix dysplasia" raises the possibility that the described phenomena may reflect the same entity. Increased awareness of the distinct histologic picture associated with VATS will likely lead to more frequent diagnosis of this underrecognized entity.

Virus‐Associated Trichodysplasia Spinulosa

Background: Virus‐associated trichodysplasia spinulosa (VATD) is a relatively new entity associated with a distinctive histologic picture of distended follicles with excessive production of inner root sheath material. Only two patients have thus far been reported. Both had developed the condition after a kidney transplant. Observation: We report two additional cases of VATD. One is a nineteen year‐old man with a history of acute lymphocytic leukemia, who developed a papular facial eruption as well as madarosis. The other is a nine year‐old boy, who presented with facial papules after a kidney transplant. Histologic examination of both cases reveals characteristic findings for trichodysplasia spinulosa, but also indicates a spectrum of histologic alterations. Ultrastructural studies confirm the presence of a variable number of intranuclear viral particles. Conclusions: Our cases illustrate the histologic spectrum seen in association with VATD. The severity of histologic alterations corresponds to the viral load seen by electron microscopy. This report documents for the first time that VATD can be found in patients without a solid organ transplant. Increased awareness of the distinct histologic picture associated with VATD will likely lead to more frequent diagnosis of this under‐recognized entity.

Viral-associated trichodysplasia in patients who are immunocompromised

Viral-associated trichodysplasia of immunosuppression is a newly described clinicopathologic entity found in patients who are undergoing drug-induced immunosuppression to prevent organ transplant rejection. Patients have numerous erythematous papules concentrated in the central portion of the face and variable degrees of hair loss, most severely affecting facial hair. Histologic findings of facial papules are highly distinctive and unique, and suggest that the entire machinery of the follicular bulb is devoted to the manufacture of inner root sheath-type keratin. Electron microscopy reveals intranuclear viral particles, but precise viral identification has not yet been achieved.