Novel betaherpesviruses and gammaherpesviruses in bats from central China.

Herpesviruses are large double-stranded DNA viruses that cause infections in animals and humans with a characteristic of latent infectious within specific tissues. Bats are natural hosts of variety human-infecting viruses and recently have been described as hosts for herpesviruses in several countries around the world. In this study we collected 140 insectivorous bats in the neighboring urban areas of Wuhan City, Hubei Province in the central China between 2020 and 2021. Nested PCR targeting the dpol gene sequence indicated that a total of 22 individuals (15.7% of the sample) tested positive for herpesvirus with 4 strains belonging to the genus Betaherpesvirus and the remaining 18 strains classified as Gammahersvirus. Furthermore, the herpesvirus prevalence in Rhinolophus pusillus was higher at 26.3%, compared to 8.4% in Myotis davidii. The RP701 strain from R. pusillus was the predominant gammaherpesvirus strain detected in bats, accounting for 94.4% (17/18) of all strains. The variations in γ-herpesviruses genomic sequences was evident in phylogenetic tree, where RP701 strain was clustered together with ruminant γ-herpesviruses, while MD704 strain formed a distinct clade with a hedgehog γ-herpesvirus. Four betaherpesviruses exclusively identified from M. davidii, with nucleotide identities ranging from 79.7 to 82.6% compared to known betaherpesviruses. Our study provided evidence that M. davidii can sever as natural host for ß-herpesviruses, which extended the host species range. In conclusion, we found that bats from central China harbored novel ß-herpesviruses and γ-herpesviruses which were phylogenetically related to ruminant γ-herpesvirus and hedgehog γ-herpesvirus. Our study indicates that bats are natural hosts of ß- and γ-herpesviruses and further studies are needed to determine whether there is cross-species transmission of herpesviruses between bats and other animals, or humans.

Epidemiology and biology of a herpesvirus in rabies endemic vampire bat populations.

Rabies is a viral zoonosis transmitted by vampire bats across Latin America. Substantial public health and agricultural burdens remain, despite decades of bats culls and livestock vaccinations. Virally vectored vaccines that spread autonomously through bat populations are a theoretically appealing solution to managing rabies in its reservoir host. We investigate the biological and epidemiological suitability of a vampire bat betaherpesvirus (DrBHV) to act as a vaccine vector. In 25 sites across Peru with serological and/or molecular evidence of rabies circulation, DrBHV infects 80-100% of bats, suggesting potential for high population-level vaccine coverage. Phylogenetic analysis reveals host specificity within neotropical bats, limiting risks to non-target species. Finally, deep sequencing illustrates DrBHV super-infections in individual bats, implying that DrBHV-vectored vaccines might invade despite the highly prevalent wild-type virus. These results indicate DrBHV as a promising candidate vector for a transmissible rabies vaccine, and provide a framework to discover and evaluate candidate viral vectors for vaccines against bat-borne zoonoses.

Discovery of herpesviruses in Canadian wildlife.

Herpesviruses (HVs) have a wide range of hosts in the animal kingdom. The result of infection with HVs can vary from asymptomatic to fatal diseases depending on subtype, strain, and host. To date, little is known about HVs naturally circulating in wildlife species and the impact of these viruses on other species. In our study, we used genetic and comparative approaches to increase our understanding of circulating HVs in Canadian wildlife. Using nested polymerase chain reaction targeting a conserved region of the HV DNA polymerase gene, we analyzed material derived from wildlife of western and northern Canada collected between February 2009 and Sept 2014. For classification of new virus sequences, we compared our viral sequences with published sequences in GenBank to identify conserved residues and motifs that are unique to each subfamily, alongside phylogenetic analysis. All alphaherpesviruses shared a conserved tryptophan (W856) and tyrosine (Y880), betaherpesviruses all shared a serine (S836), and gammaherpesviruses had a conserved glutamic acid (E835). Most of our wildlife HV sequences grouped together with HVs from taxonomically related host species. From Martes americana, we detected previously uncharacterized alpha- and beta-herpesviruses.

Identification of Novel Betaherpesviruses in Iberian Bats Reveals Parallel Evolution.

A thorough search for bat herpesviruses was carried out in oropharyngeal samples taken from most of the bat species present in the Iberian Peninsula from the Vespertilionidae, Miniopteridae, Molossidae and Rhinolophidae families, in addition to a colony of captive fruit bats from the Pteropodidae family. By using two degenerate consensus PCR methods targeting two conserved genes, distinct and previously unrecognized bat-hosted herpesviruses were identified for the most of the tested species. All together a total of 42 potentially novel bat herpesviruses were partially characterized. Thirty-two of them were tentatively assigned to the Betaherpesvirinae subfamily while the remaining 10 were allocated into the Gammaherpesvirinae subfamily. Significant diversity was observed among the novel sequences when compared with type herpesvirus species of the ICTV-approved genera. The inferred phylogenetic relationships showed that most of the betaherpesviruses sequences fell into a well-supported unique monophyletic clade and support the recognition of a new betaherpesvirus genus. This clade is subdivided into three major clades, corresponding to the families of bats studied. This supports the hypothesis of a species-specific parallel evolution process between the potentially new betaherpesviruses and their bat hosts. Interestingly, two of the betaherpesviruses' sequences detected in rhinolophid bats clustered together apart from the rest, closely related to viruses that belong to the Roseolovirus genus. This suggests a putative third roseolo lineage. On the contrary, no phylogenetic structure was detected among several potentially novel bat-hosted gammaherpesviruses found in the study. Remarkably, all of the possible novel bat herpesviruses described in this study are linked to a unique bat species.

Elephant endotheliotropic herpesviruses EEHV1A, EEHV1B, and EEHV2 from cases of hemorrhagic disease are highly diverged from other mammalian herpesviruses and may form a new subfamily.

UNLABELLED: A family of novel endotheliotropic herpesviruses (EEHVs) assigned to the genus Proboscivirus have been identified as the cause of fatal hemorrhagic disease in 70 young Asian elephants worldwide. Although EEHV cannot be grown in cell culture, we have determined a total of 378 kb of viral genomic DNA sequence directly from clinical tissue samples from six lethal cases and two survivors. Overall, the data obtained encompass 57 genes, including orthologues of 32 core genes common to all herpesviruses, 14 genes found in some other herpesviruses, plus 10 novel genes, including a single large putative transcriptional regulatory protein (ORF-L). On the basis of differences in gene content and organization plus phylogenetic analyses of conserved core proteins that have just 20% to 50% or less identity to orthologues in other herpesviruses, we propose that EEHV1A, EEHV1B, and EEHV2 could be considered a new Deltaherpesvirinae subfamily of mammalian herpesviruses that evolved as an intermediate branch between the Betaherpesvirinae and Gammaherpesvirinae. Unlike cytomegaloviruses, EEHV genomes encode ribonucleotide kinase B subunit (RRB), thymidine kinase (TK), and UL9-like origin binding protein (OBP) proteins and have an alphaherpesvirus-like dyad symmetry Ori-Lyt domain. They also differ from all known betaherpesviruses by having a 40-kb large-scale inversion of core gene blocks I, II, and III. EEHV1 and EEHV2 DNA differ uniformly by more than 25%, but EEHV1 clusters into two major subgroups designated EEHV1A and EEHV1B with ancient partially chimeric features. Whereas large segments are nearly identical, three nonadjacent loci totaling 15 kb diverge by between 21 and 37%. One strain of EEHV1B analyzed is interpreted to be a modern partial recombinant with EEHV1A. IMPORTANCE: Asian elephants are an endangered species whose survival is under extreme pressure in wild range countries and whose captive breeding populations in zoos are not self-sustaining. In 1999, a novel class of herpesviruses called EEHVs was discovered. These viruses have caused a rapidly lethal hemorrhagic disease in 20% of all captive Asian elephant calves born in zoos in the United States and Europe since 1980. The disease is increasingly being recognized in Asian range countries as well. These viruses cannot be grown in cell culture, but by direct PCR DNA sequence analysis from segments totaling 15 to 30% of the genomes from blood or necropsy tissue from eight different cases, we have determined that they fall into multiple types and chimeric subtypes of a novel Proboscivirus genus, and we propose that they should also be classified as the first examples of a new mammalian herpesvirus subfamily named the Deltaherpesvirinae.

Trunkloads of viruses.

Elephant populations are under intense pressure internationally from habitat destruction and poaching for ivory and meat. They also face pressure from infectious agents, including elephant endotheliotropic herpesvirus 1 (EEHV1), which kills ~20% of Asian elephants (Elephas maximus) born in zoos and causes disease in the wild. EEHV1 is one of at least six distinct EEHV in a phylogenetic lineage that appears to represent an ancient but newly recognized subfamily (the Deltaherpesvirinae) in the family Herpesviridae.

Comparative genome analysis of four elephant endotheliotropic herpesviruses, EEHV3, EEHV4, EEHV5, and EEHV6, from cases of hemorrhagic disease or viremia.

UNLABELLED: The genomes of three types of novel endotheliotropic herpesviruses (elephant endotheliotropic herpesvirus 1A [EEHV1A], EEHV1B, and EEHV2) associated with lethal hemorrhagic disease in Asian elephants have been previously well characterized and assigned to a new Proboscivirus genus. Here we have generated 112 kb of DNA sequence data from segments of four more types of EEHV by direct targeted PCR from blood samples or necropsy tissue samples from six viremic elephants. Comparative phylogenetic analysis of nearly 30 protein-encoding genes of EEHV5 and EEHV6 show that they diverge uniformly by nearly 20% from their closest relatives, EEHV2 and EEHV1A, respectively, and are likely to have similar overall gene content and genome organization. In contrast, seven EEHV3 and EEHV4 genes analyzed differ from those of all other EEHVs by 37% and have a G+C content of 63% compared to just 42% for the others. Three strains of EEHV5 analyzed clustered into two partially chimeric subgroups EEHV5A and EEHV5B that diverge by 19% within three small noncontiguous segments totaling 6.2 kb. We conclude that all six EEHV types should be designated as independent species within a proposed new fourth Deltaherpesvirinae subfamily of mammalian herpesviruses. These virus types likely initially diverged close to 100 million years ago when the ancestors of modern elephants split from all other placental mammals and then evolved into two major branches with high- or low-G+C content about 35 million years ago. Later additional branching events subsequently generated three paired sister taxon lineages of which EEHV1 plus EEHV6, EEHV5 plus EEHV2, and EEHV4 plus EEHV3 may represent Asian and African elephant versions, respectively. IMPORTANCE: One of the factors threatening the long-term survival of endangered Asian elephants in both wild range countries and in captive breeding populations in zoos is a highly lethal hemorrhagic herpesvirus disease that has killed at least 70 young Asian elephants worldwide. The genomes of the first three types of EEHVs (or probosciviruses) identified have been partially characterized in the preceding accompanying paper (L. K. Richman, J.-C. Zong, E. M. Latimer, J. Lock, R. C. Fleischer, S. Y. Heaggans, and G. S. Hayward, J. Virol. 88:13523-13546, 2014, http://dx.doi.org/10.1128/JVI.01673-14). Here we have used PCR DNA sequence analysis from multiple segments of DNA amplified directly from blood or necropsy tissue samples of six more selected cases of hemorrhagic disease to partially characterize four other types of EEHVs from either Asian or African elephants. We propose that all six types and two chimeric subtypes of EEHV belong to multiple lineages of both AT-rich and GC-rich branches within a new subfamily to be named the Deltaherpesvirinae, which evolved separately from all other mammalian herpesviruses about100 million years ago.

Orofacial viral infections--an update for clinicians.

UNLABELLED: Orofacial viral infections may be less common but appear in different clinical forms. Often these infections get initially treated by antibiotics which obviously will have limited or no effect. The authors review the current concepts of orofacial viral infections, causative agents, their classification and clinical manifestations and a basis for treatment. CLINICAL RELEVANCE: Most viral infections do not require any specific treatment except in patients who are immunosuppressed or immunodeficient. Appropriate diagnosis and timely management of orofacial viral lesions are important irrespective of whether it is localized or a manifestation of a systemic infection.

Complete genome sequences of elephant endotheliotropic herpesviruses 1A and 1B determined directly from fatal cases.

A highly lethal hemorrhagic disease associated with infection by elephant endotheliotropic herpesvirus (EEHV) poses a severe threat to Asian elephant husbandry. We have used high-throughput methods to sequence the genomes of the two genotypes that are involved in most fatalities, namely, EEHV1A and EEHV1B (species Elephantid herpesvirus 1, genus Proboscivirus, subfamily Betaherpesvirinae, family Herpesviridae). The sequences were determined from postmortem tissue samples, despite the data containing tiny proportions of viral reads among reads from a host for which the genome sequence was not available. The EEHV1A genome is 180,421 bp in size and consists of a unique sequence (174,601 bp) flanked by a terminal direct repeat (2,910 bp). The genome contains 116 predicted protein-coding genes, of which six are fragmented, and seven paralogous gene families are present. The EEHV1B genome is very similar to that of EEHV1A in structure, size, and gene layout. Half of the EEHV1A genes lack orthologs in other members of subfamily Betaherpesvirinae, such as human cytomegalovirus (genus Cytomegalovirus) and human herpesvirus 6A (genus Roseolovirus). Notable among these are 23 genes encoding type 3 membrane proteins containing seven transmembrane domains (the 7TM family) and seven genes encoding related type 2 membrane proteins (the EE50 family). The EE50 family appears to be under intense evolutionary selection, as it is highly diverged between the two genotypes, exhibits evidence of sequence duplications or deletions, and contains several fragmented genes. The availability of the genome sequences will facilitate future research on the epidemiology, pathogenesis, diagnosis, and treatment of EEHV-associated disease.

Detection and evaluation of novel herpesviruses in routine and pathological samples from Asian and African elephants: identification of two new probosciviruses (EEHV5 and EEHV6) and two new gammaherpesviruses (EGHV3B and EGHV5).

Systemic infections with elephant endotheliotropic herpesviruses (EEHV) cause a rapid onset acute hemorrhagic disease with an 85% mortality rate. More than 60 cases have been confirmed worldwide occurring predominantly in juvenile Asian elephants. Originally, three virus types EEHV1A, EEHV1B and EEHV2 were identified, all members of the Proboscivirus genus within the Betaherpesvirinae. However, four elephant gammaherpesviruses (EGHV) have also been found by DNA PCR approaches in eye and genital secretions of asymptomatic animals, and two more versions of the probosciviruses, EEHV3 and EEHV4, were recently detected in acute hemorrhagic disease cases. To ask whether even more species of elephant herpesviruses may exist, we have developed several new diagnostic DNA PCR assays using multiple round primers in the DNA POL region. These have been used routinely for nearly three years to screen samples submitted to the Elephant Herpesvirus Laboratory for diagnosis of possible cases of EEHV disease in blood and necropsy tissue, as well as in biopsies of other suspicious lesions or growths. Several more cases of EEHV1-associated hemorrhagic disease were confirmed, but in addition, we describe here eleven examples of other known and novel herpesviruses detected and evaluated with these reagents. They include the prototypes of four new elephant herpesviruses, two more within the proboscivirus group EEHV5 and EEHV6, plus two more gammaherpesviruses EGHV3B and EGHV5. We also report initial semi-quantitative PCR assays demonstrating very high viral loads in the blood of the EEHV3 and EEHV4-associated hemorrhagic disease cases.

Identification of a novel betaherpesvirus in Mus musculus.

Rodent betaherpesviruses vary considerably in genomic content, and these variations can result in a distinct pathogenicity. Therefore, the identification of unknown betaherpesviruses in house mice (Mus musculus), the most important rodent host species in basic research, is of importance. During a search for novel herpesviruses in house mice using herpesvirus consensus PCR and attempts to isolate viruses in tissue culture, we identified a previously unknown betaherpesvirus. The primary PCR search in mouse organs revealed the presence of known strains of murine cytomegalovirus (Murid herpesvirus 1) and of Mus musculus rhadinovirus 1 only. However, the novel virus was detected after incubation of organ pieces in fibroblast tissue culture and subsequent PCR analysis of the supernatants. Long-distance PCR amplification including the DNA polymerase and glycoprotein B genes revealed a 3.4 kb sequence that was similar to sequences of rodent cytomegaloviruses. Pairwise sequence comparisons and phylogenetic analyses showed that this newly identified murine virus is most similar to the English isolate of rat cytomegalovirus, thereby raising the possibility that two distinct CMV lineages have evolved in both Mus musculus and Rattus norvegicus.

Analysis of the nucleotide sequence of the guinea pig cytomegalovirus (GPCMV) genome.

In this report we describe the genomic sequence of guinea pig cytomegalovirus (GPCMV) assembled from a tissue culture-derived bacterial artificial chromosome clone, plasmid clones of viral restriction fragments, and direct PCR sequencing of viral DNA. The GPCMV genome is 232,678 bp, excluding the terminal repeats, and has a GC content of 55%. A total of 105 open reading frames (ORFs) of > 100 amino acids with sequence and/or positional homology to other CMV ORFs were annotated. Positional and sequence homologs of human cytomegalovirus open reading frames UL23 through UL122 were identified. Homology with other cytomegaloviruses was most prominent in the central approximately 60% of the genome, with divergence of sequence and lack of conserved homologs at the respective genomic termini. Of interest, the GPCMV genome was found in many cases to bear stronger phylogenetic similarity to primate CMVs than to rodent CMVs. The sequence of GPCMV should facilitate vaccine and pathogenesis studies in this model of congenital CMV infection.

Discovery of herpesviruses in bats.

Seven novel gammaherpesviruses (GHV) and one novel betaherpesvirus were discovered in seven different European bat species (order Chiroptera, family Vespertilionidae) with a pan-herpesvirus PCR assay, targeting the DNA polymerase (DPOL) gene. The sequences of six bat GHV were similarly related to members of the gammaherpesvirus genera Percavirus and Rhadinovirus. The seventh GHV was related to the porcine lymphotropic herpesvirus 1 (genus Macavirus). The betaherpesvirus appeared to be a distant relative of human cytomegalovirus. For three bat GHV a 3.6 kbp locus was amplified and sequenced, spanning part of the glycoprotein B gene and the majority of the DPOL gene. In phylogenetic analysis, the three bat GHV formed a separate clade with similar distance to the Percavirus and Rhadinovirus clades. These novel viruses are the first herpesviruses to be described in bats.

Analysis and characterization of the complete genome of tupaia (tree shrew) herpesvirus.

The tupaia herpesvirus (THV) was isolated from spontaneously degenerating tissue cultures of malignant lymphoma, lung, and spleen cell cultures of tree shrews (Tupaia spp.). The determination of the complete nucleotide sequence of the THV strain 2 genome resulted in a 195,857-bp-long, linear DNA molecule with a G+C content of 66.5%. The terminal regions of the THV genome and the loci of conserved viral genes were found to be G+C richer. Furthermore, no large repetitive DNA sequences could be identified. This is in agreement with the previous classification of THV as the prototype species of herpesvirus genome group F. The search for potential coding regions resulted in the identification of 158 open reading frames (ORFs) regularly distributed on both DNA strands. Seventy-six out of the 158 ORFs code for proteins that are significantly homologous to known herpesvirus proteins. The highest homologies found were to primate and rodent cytomegaloviruses. Biological properties, protein homologies, the arrangement of conserved viral genes, and phylogenetic analysis revealed that THV is a member of the subfamily Betaherpesvirinae. The evolutionary lineages of THV and the cytomegaloviruses seem to have branched off from a common ancestor. In addition, it was found that the arrangements of conserved genes of THV and murine cytomegalovirus strain Smith, both of which are not able to form genomic isomers, are colinear with two different human cytomegalovirus (HCMV) strain AD169 genomic isomers that differ from each other in the orientation of the long unique region. The biological properties and the high degree of relatedness of THV to the mammalian cytomegaloviruses allow the consideration of THV as a model system for investigation of HCMV pathogenicity.

Structural organization and analysis of the viral terminase gene locus of Tupaia herpesvirus.

Tupaia herpesvirus (THV) was isolated from spontaneously degenerating tissue cultures of malignant lymphoma, lung, and spleen cell cultures of tree shrews (Tupaia spp.). In order to determine the phylogenetic relatedness of THV the complete nucleotide sequence of the viral terminase (VTER) gene locus (6223 bp) of Tupaia herpesvirus strain 2 (THV-2) was elucidated and analysed. The VTER gene locus, encoding one of the most highly conserved herpes viral proteins is composed of two exons. The intron contains five potential open reading frames (ORFs). The arrangement of these ORFs is colinear with the corresponding regions in the genomes of the mammalian cytomegaloviruses. The precise primary structure of the THV-2 VTER splice junction was determined using RT-PCR and was found to be in agreement with the corresponding splice donor and acceptor sites of the mammalian cytomegaloviruses. The comparison of all six putative THV-2 proteins with the corresponding counterparts in other herpesviruses revealed that THV resides between the Human and the Murine cytomegalovirus (HCMV, MCMV). These results are in agreement with our previous statement, that THV and the known cytomegaloviruses are closely related to each other and should be classified into one taxonomic group. The genetic data presented here and in previous studies are based on the detailed comparison of highly conserved viral genes. Consequently, the classification of the Human and the cytomegaloviruses into the two genera Cyto- and Muromegalovirus, that is mainly based on overall genome structure, should be reconsidered.

Gene content phylogeny of herpesviruses.

Clusters of orthologous groups [COGs; Tatusov, R. L., Koonin, E. V. & Lipman, D. J. (1997) Science 278, 631-637] were identified for a set of 13 completely sequenced herpesviruses. Each COG represented a family of gene products conserved across several herpes genomes. These families were defined without using an arbitrary threshold criterion based on sequence similarity. The COG technique was modified so that variable stringency in COG construction was possible. High stringencies identify a core set of highly conserved genes. Varying COG stringency reveals differences in the degree of conservation between functional classes of genes. The COG data were used to construct whole-genome phylogenetic trees based on gene content. These trees agree well with trees based on other methods and are robust when tested by bootstrap analysis. The COG data also were used to construct a reciprocal tree that clustered genes with similar phylogenetic profiles. This clustering may give clues to genes with related functions or with related histories of acquisition and loss during herpesvirus evolution.

The Maastricht strain and England strain of rat cytomegalovirus represent different betaherpesvirus species rather than strains.

The major immediate early (MIE) locus of the Maastricht strain of rat cytomegalovirus (RCMV) was found to comprise five exons of which the first is noncoding. The first three exons are spliced to either exon 4, generating IE1, or exon 5, generating IE2. An additional splicing event unique to RCMV (Maastricht) was identified in exon 5, resulting in a 466-bp deletion. IE1 transcripts were detected exclusively during the IE phase of infection in vitro, whereas IE2 transcripts were detected during both the IE and late phase of infection. The similarities between amino acid sequences derived from the MIE gene of RCMV (Maastricht) and murine cytomegalovirus are low (22 and 37% for IE1 and IE2, respectively). Surprisingly, the similarities between the MIE proteins of RCMV (Maastricht) and the England strain of RCMV are also low (23 and 32% for IE1 and IE2, respectively). This suggests that these RCMV strains represent different betaherpesvirus species rather than strains. This is underscored by the difference between both viruses in genome size as well as growth characteristics. The existence of two different RCMV-like species might have important implications for the use of these viruses as models for human cytomegalovirus.

Identification and characterization of the Tupaia herpesvirus DNA polymerase gene.

Tupaia herpesviruses (THVs) have been isolated from malignant lymphomas and from degenerating lung or spleen cell cultures of tree shrews (Tupoia spp.), but because of a lack of genetic information the final classification of THVs is still open. In the present work the viral DNA polymerase (DPOL) gene was mapped within the genome of the different THV strains using PCR and degenerate oligonucleotide primers. Nucleotide sequences of the DPOL genes of THV strains 1 to 5 were determined and used for comparative analyses. The transcriptional activity of the THV-2 DPOL gene was confirmed by RT-PCR. It was found that the different THV strains are very closely related to each other. When compared to other herpesviruses the highest amino acid sequence identities detected were with DPOLs of the murine and human cytomegaloviruses. These results justify the conclusion that THVs are members of the subfamily Betaherpes-virinae.

Infección congénita por citomegalovirus

El citomegalovirus (CMV) se encuentra ampliamente distribuido en la población, es el responsable de graves infecciones especialmente congénitas y es considerado como un problema médico-biológico debido al poco conocimiento de la epidemiología de la infección latente (1-5). El CMV es un ADN virus miembro de la subfamilia Betaherpesvirinae, con una gran capacidad para adaptarse y permanecer latente y presentar reactivaciones en situaciones en que esté alterada la respuesta inmune, por lo que se ha considerado como un verdadero marcador de inmunodeficiencia (6-9). Su incidencia es variable, oscila entre 1 y 5 por ciento. La enfermedad por citomegalovirus es subclínica en un 90 por ciento de los casos y de éstos el 10 por ciento tienen secuelas neurológicas. El CMV ataca la matriz germinal ependimaria y la sustancia blanca produciendo lesiones de necrosis, calcificación, disgenesia cerebral, microcefalia, micropoligiria que se traduce en retardo mental, convulsiones, displejía espástica (5, 10-12). El diagnóstico no sólo es clínico, sino virológico inmunológico, histológico y escanográfico. El tratamiento es multidisciplinario y el pronóstico depende del compromiso neurológico (9, 13-15). Con el objeto de resaltar las manifestaciones neurológicas en los pacientes pediátricos infectado por el CMV, presentamos estas cuatro casos clínicos que consultaron el servicio de neurología infantil del Hospital Universitario de Cartagena.