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Hippocampal and neocortical activation during repetitive encoding in older persons.

Episodic memory function is known to decline in the course of normal aging; however, compensatory techniques can improve performance significantly in older persons. We investigated the effects of the memory enhancing technique of repetition encoding on brain activation using event-related functional magnetic resonance imaging (fMRI). Twelve healthy older adults without cognitive impairment were studied with fMRI during repetitive encoding of face-name pairs. During the first encoding trials of face-name pairs that were subsequently remembered correctly, activation of the hippocampus and multiple neocortical regions, including prefrontal, parietal and fusiform cortices, was observed. The second and third encoding trials resulted in continued activation in neocortical regions, but no task-related response within the hippocampus. Functional imaging of successful memory processes thus permits us to detect regionally specific responses in the aging brain. Our findings suggest that hippocampal function is preserved in normal aging and that repetition-based memory enhancing techniques may engage primarily neocortical attentional networks.

Age Factors↗

Effects of aging on transient and sustained successful memory encoding activity.

Event-related fMRI studies have investigated age-related changes in encoding by identifying greater activity for items that are later remembered than for those that are forgotten (difference in memory, or Dm). The present study used hybrid blocked/event-related analyses to distinguish between transient Dm versus sustained Dm. Dm was identified as parametric increases in encoding activity as a function of a combined subsequent memory/confidence scale. Dm was measured in each trial (transient activity) and in blocks of eight trials (sustained activity). Transient Dm analyses showed age-related reductions in the left hippocampus but increases in left prefrontal cortex (PFC). Sustained Dm analyses showed age-related reductions in right PFC, but no region showing increased activity in older adults. These findings suggests that during semantic classification older adults show less spontaneous hippocampal-mediated encoding processes, but greater PFC-mediated semantic processes. Additionally, the decline in sustained Dm in PFC may involve age-related deficits in sustained attention that impact encoding processes. The results underscore the importance of investigating aging effects on both transient and sustained neural activity.

Adaptation, Physiological↗

Orbitofrontal contribution to auditory encoding.

Having recently demonstrated that the human orbitofrontal cortex is selectively activated during the encoding of visual information, we investigated whether this same frontal region, which is directly connected to medial temporal structures, would be activated during the encoding of auditory stimuli. We measured cerebral blood flow (CBF) with positron emission tomography (PET) during the encoding of nonverbal abstract auditory stimuli in a group of young healthy volunteers. The results demonstrate that the left orbitofrontal cortex, area 11 in particular, is involved in the encoding of auditory information. We suggest that the orbitofrontal cortex is a critical frontal region that can exert top-down regulation of other regions of the brain including the medial temporal structures and the lateral frontal cortex, enabling the further processing of information.

Acoustic Stimulation↗

Positive or negative blips? The effect of phase encoding scheme on susceptibility-induced signal losses in EPI.

The observation of blood oxygenation level-dependent (BOLD) effect in functional magnetic resonance imaging (fMRI) studies is often hampered by the presence of magnetic field inhomogeneities. These are caused by abrupt changes in the magnetic susceptibility that typically occur near air/tissue interfaces and may result in substantial image distortions and signal losses. In this article, we investigate the effect of susceptibility-induced magnetic field inhomogeneities on the signal intensity (I) and the BOLD sensitivity (BS) for two different phase encoding schemes in blipped echo-planar imaging (EPI), which use either positive (EPIpos) or negative (EPIneg) phase gradient blips for stepping through k-space. Based on magnetic field maps, we generate computer simulations of I and BS for both phase encoding schemes and demonstrate good agreement with the experimental image intensities. We show that regions compromised by susceptibility effects are affected very differently by EPIpos and EPIneg. Further simulations are performed in two representative regions of interest (orbitofrontal cortex and lower temporal lobe) to investigate the dependence of I and BS on the slice angle (alpha), the magnitude of a moderate compensation gradient applied in the slice direction (GScomp), and the phase encoding scheme. We find that I and BS can be considerably increased if the appropriate phase encoding scheme is applied in addition to optimizing alpha and GScomp. Our results suggest that this optimization method would be useful in future fMRI studies to improve the sensitivity in regions compromised by susceptibility effects.

Artifacts↗

Hippocampal activations during encoding and retrieval in a verbal working memory paradigm.

Though the hippocampus has been associated with encoding and retrieval processes in episodic memory, the precise nature of its involvement in working memory has yet to be determined. This functional magnetic resonance imaging (fMRI) study employed a verbal working memory paradigm that allows for the within-subject comparison of functional activations during encoding, maintenance, and retrieval. In each trial, participants were shown 5 target words and, after an 8 s delay, a series of probe words. Probe words consisted of target matches, phonetically or semantically related foils, or foils unrelated to the target words. Both the left and right hippocampi showed higher mean activation amplitudes during encoding than maintenance. In contrast, the right dorsolateral prefrontal cortex (DLPFC) showed greater activation during maintenance than encoding. Both hippocampal and DLPFC regions were more active during retrieval than maintenance. Furthermore, an analysis of retrieval activation separated by probe type showed a trend toward greater bilateral hippocampal activation for probes related (both semantically and phonetically) to the target than for unrelated probes and still greater activation for target matches. This pattern suggests that there may be roles for the hippocampus and DLPFC in working memory that change as function of information processing stage. Additionally, the trend towards increased involvement of the hippocampus with the increase in relatedness of the probe stimuli to the information maintained is interpreted to be consistent with the role of the hippocampus in recollection-based retrieval in long-term memory and may indicate that this role extends to working memory processes.

Adult↗

Encoding a motor memory in the older adult by action observation.

The ability of motor training to encode a motor memory is reduced in older adults. Here, we tested the hypothesis that training-dependent memory encoding, an issue of relevance in neurorehabilitation, is enhanced in elder individuals by action observation which alone can contribute to learning processes. A group of 11 healthy older adults participated in this study, which consisted of three randomized counterbalanced sessions on different days testing the effects of motor training (MT) alone, action observation (AO) alone, and a combination of both (MT + AO) on motor memory encoding. The combination of MT + AO formed a motor memory in the primary motor cortex and differentially modulated motor cortical excitability in muscles that were agonist and antagonist with respect to the training task, but MT or AO alone did not. These results suggest that action observation can enhance the effects of motor training on memory encoding protocols in the older adult, possibly through Hebbian modulation of intracortical excitatory mechanisms.

Aged↗

Prefrontal activity during taste encoding: an fNIRS study.

To elucidate the function of the lateral prefrontal cortex (LPFC) in taste encoding, it is worth applying to taste, the psychological paradigms of intentional memorization that have been used with other extensively studied senses, and thus updating current models for LPFC functions to include a taste modality. Using multichannel functional near-infrared spectroscopy (fNIRS), we examined the LPFC's of healthy volunteers (N = 18) during the intentional memorization of a basic taste. In order to minimize the confounding effects of verbal processes that are known to employ the left LPFC, we used quaternary taste mixtures that were difficult to verbalize, and confined analysis to those who did not use a verbal strategy during memorization (N = 10). In order to examine the results in association with data in the literature, the location of activity was probabilistically estimated and anatomically labeled in the Montreal Neurological Institute (MNI) standard brain space. By contrasting the cortical activation under encoding conditions with that under control conditions without memory requirement, we found activation in the bilateral ventro-LPFC and the right posterior portion of the LPFC. The activation pattern was consistent with previous studies on the encoding of nonverbal materials using other senses. This suggests that models for LPFC functions that derive from previous studies can be generalized to intentional encoding processes of taste information, at least at a macro-structural level. The current study also demonstrates that, by using fNIRS, LPFC functions on taste can be examined with experimental paradigms relevant to those used for other senses.

Adult↗

Mice expressing constitutively active Gsalpha exhibit stimulus encoding deficits similar to those observed in schizophrenia patients.

People with schizophrenia display sensory encoding deficits across a broad range of electrophysiological and behavioral measures, suggesting fundamental impairments in the ability to transduce the external environment into coherent neural representations. This inability to create basic components of complex stimuli interferes with a high fidelity representation of the world and likely contributes to cognitive deficits. The current study evaluates the effects of constitutive forebrain activation of the G(s)alpha G-protein subunit on auditory threshold and gain using acoustic brainstem responses and cortically generated N40 event-related potentials to assess the role of cyclic AMP signaling in sensory encoding. Additionally, we examine the ability of pharmacological treatments that mimic (amphetamine) or ameliorate (haloperidol) positive symptoms of schizophrenia to test the hypothesis that the encoding deficits observed in G(s)alpha transgenic mice can be normalized with treatment. We find that G(s)alpha transgenic mice have decreased amplitude of cortically generated N40 but normal acoustic brainstem response amplitude, consistent with forebrain transgene expression and a schizophrenia endophenotype. Transgenic mice also display decreased stimulus intensity response (gain) in both acoustic brainstem response and N40, indicating corticofugal influence on regions that lack transgene expression. N40 deficits in transgenic animals were ameliorated with low dose haloperidol and reversed with higher dose, suggesting dopamine D2 receptor-linked Gi activity contributes to the impairment. Consistent with this hypothesis, we recreated the G(s)alpha transgenic deficit in wild type animals using the indirect dopamine agonist amphetamine. This transgenic model of sensory encoding deficits provides a foundation for identifying biochemical contributions to sensory processing impairments associated with schizophrenia.

Acoustic Stimulation↗

Medial temporal and prefrontal lobe activation during verbal encoding following glucose ingestion in schizophrenia: A pilot fMRI study.

Verbal declarative memory is one of the most reliably impaired cognitive functions in schizophrenia. Important issues are whether the problem is reversible, and which brain regions underlie improvement. We showed previously that glucose administration improved declarative memory in patients with schizophrenia, and sought in this pilot study to identify whether glucose affects the location or degree of activation of brain regions involved in a verbal encoding task. Seven clinically stable and medicated patients with schizophrenia or schizoaffective disorder, who showed deficits on a clinical test of memory, participated in the study. Subjects served as their own controls in a double-blind, crossover protocol that consisted of two sessions about a week apart. In each session, subjects ingested a beverage flavored with lemonade that contained 50 g of glucose on one occasion, and saccharin on the other. Blood glucose was measured before and 15, 50, and 75 min after ingestion. After ingesting the beverage, they performed a verbal encoding task while undergoing brain functional magnetic resonance imaging. The results showed significantly greater activation of the left parahippocampus during novel sentence encoding in the glucose condition, compared to the saccharin condition, despite no change in memory performance. A trend towards greater activation of the left dorsolateral prefrontal cortex (p<.07) was also evident in the glucose condition. These pilot findings emphasize the sensitivity of both the medial temporal and prefrontal regions to effects of glucose administration during encoding, and are consistent with the hypothesis that these regions also participate in declarative memory improvements following glucose administration.

Administration, Oral↗

Hippocampal CA1 spiking during encoding and retrieval: relation to theta phase.

The hippocampal theta rhythm is a prominent oscillation in the field potential observed throughout the hippocampus as a rat investigates stimuli in the environment. A recent computational model [Hasselmo, M. E., Bodelon, C., & Wyble, B. P. (2002a). A proposed function for hippocampal theta rhythm: separate phases of encoding and retrieval enhance reversal of prior learning. Neural Computation, 14, 793-817. Neuromodulation, theta rhythm and rat spatial navigation. Neural Networks, 15, 689-707] suggested that the theta rhythm allows the hippocampal formation to alternate rapidly between conditions that promote memory encoding (strong synaptic input from entorhinal cortex to areas CA3 and CA1) and conditions that promote memory retrieval (strong synaptic input from CA3 to CA1). That model predicted that the preferred theta phase of CA1 spiking should differ for information being encoded versus information being retrieved. In the present study, the spiking activity of CA1 pyramidal cells was recorded while rats performed either an odor-cued delayed nonmatch-to-sample recognition memory test or an object recognition memory task based on the animal's spontaneous preference for novelty. In the test period of both tasks, the preferred theta phase exhibited by CA1 pyramidal cells differed between moments when the rat inspected repeated (match) and non-repeated (nonmatch) items. Also in the present study, additional modeling work extended the previous model to address the mean phase of CA1 spiking associated with stimuli inducing varying levels of retrieval relative to encoding, ranging from novel nonmatch stimuli with no retrieval to highly familiar repeated stimuli with extensive retrieval. The modeling results obtained here demonstrated that the experimentally observed phase differences are consistent with different levels of CA3 synaptic input to CA1 during recognition of repeated items.

Animals↗

Expression of mRNA encoding insulin-like growth factor binding protein-2 (IGFBP-2) during induced and natural regression of equine corpora lutea.

The insulin-like growth factors, IGF-I and -II, have been shown to play a key role in luteal function in some species. The IGF binding proteins, IGFBP-2 and -3, have been shown to inhibit binding of IGF-I and -II to bovine luteal cells and decrease progesterone production. We have recently shown that equine follicles have the genetic capacity to produce IGFBP-2, and that levels decrease in healthy preovulatory follicles. In the present study expression of mRNAs encoding IGFBP-2, as well as the rate-limiting steroidogenic enzyme, P450scc, were studied in equine corpora lutea to investigate whether IGFBP-2 might be involved in luteolysis. Corpora lutea were collected from mares in mid-luteal phase (day 10), at early regression (day 14), late regression (day 17), and 12 and 36 h after intramuscular administration of the PGF(2alpha) analogue, cloprostenol (0.5 microg/kg). During early natural regression, and 12 h after administration of cloprostenol on day 10, steady state levels of mRNAs encoding P450scc had decreased significantly compared with day 10 of dioestrus (P < 0.001). Levels of mRNA encoding IGFBP-2 increased significantly between mid-diestrus and early (P < 0.01) and late (P < 0.001) regression, and 36 h after cloprostenol administration (P < 0.001). We conclude that the genetic capacity for increased IGFBP-2 production in the early stages of natural luteolysis in the mare may act to sequester IGF-I in the CL, assisting in inhibition of progesterone production. However the delay in increase in mRNA encoding IGFBP-2 after cloprostenol administration, combined with the sharp fall in expression of P450scc mRNA, suggests that the luteolytic action of a pharmacological dose of cloprostenol may not be mediated via IGFBP-2 in the mare.

Animals↗

HCMV-encoded G-protein-coupled receptors as constitutively active modulators of cellular signaling networks.

Several herpesviruses encode G-protein-coupled receptor (vGPCR) proteins that are homologous to human chemokine receptors. In contrast to chemokine receptors, many vGPCRs signal in a ligand-independent (constitutive) manner. Such constitutive signaling is of major significance because various pathologies are associated with activating GPCR mutations. Constitutive activity of the human herpesvirus 8-encoded GPCR (ORF74), for example, is essential for its oncogenic potential to cause angioproliferative Kaposi's sarcoma-like lesions. The human cytomegalovirus (HCMV) encodes four GPCRs, of which US28 and UL33 display constitutive activity in transfected, but also HCMV-infected, cells. In addition, US28 is activated by a broad spectrum of chemokines. Furthermore, both US28 and UL33 show promiscuous G-protein coupling, whereas chemokine receptors activate primarily G(i/o) proteins. Thus, these vGPCRs are versatile signaling devices, reprogramming cellular signaling networks to modulate cellular function after infection. By these means, these HCMV-encoded receptors might contribute to HCMV-related pathologies.

Amino Acid Sequence↗

Immunization with a DNA chimeric molecule encoding a hemagglutinin peptide and a scFv CD21-specific antibody fragment induces long-lasting IgM and CTL responses to influenza virus.

Killed viral vaccines are known to induce primarily antibody responses. By contrast DNA vaccination using naked DNA encoding viral antigens induces both humoral and cellular immune responses. Various approaches have been used to construct DNA vaccines with build-in adjuvanticity. We hypothesized that sequences encoding a common epitope of influenza A virus hemagglutinin jointed to sequences encoding a single-chain variable fragment (scFv) antibody fragment to a costimulatory B cell surface receptor would result in the in vivo expression of a chimeric viral peptide with increased immunogenicity. Such a hybrid DNA molecule was constructed by us, encoding a T and B cell epitope-containing influenza hemagglutinin peptide and a scFv antibody fragment binding to mouse complement receptors I and II (CR1 and CR2). A single immunization with a plasmid containing the described construct induced a strong anti-influenza cytotoxic response lasting for more than six months and a weak antibody response.

Adjuvants, Immunologic↗

Co-delivery of plasmid-encoded cytokines modulates the immune response to a DNA vaccine delivered by in vivo electroporation.

In this study, in vivo electroporation of a DNA vaccine adjuvanted with plasmids encoding different cytokines was investigated in large animals. Sheep were injected intramuscularly with a DNA vaccine encoding an antigen of Haemonchus contortus (pNPA) and plasmids encoding different cytokines followed by in vivo electroporation. Plasmids (pCI) carrying the genes of different cytokines including ovine IL-4(pCI-IL4), IL-10(pCI-IL10), GM-CSF(pCI-GMCSF), and MCP-1alpha(pCI-MCP1alpha), and pCI-IL4+pCI-GMCSF were co-delivered with pNPA. The results showed that co-delivery of pCI-GMCSF or pCI-IL4+pCI-GMCSF significantly enhanced both antibody responses and T cell proliferation responses to the antigen after two DNA immunisations compared to co-delivery of pCI. In contrast, antibody responses of the sheep that received pCI-IL10 were decreased significantly. Other cytokine expressing plasmids did not significantly alter the measured immune responses. Furthermore, co-delivery of pCI-GMCSF increased IgG2 response more than IgG1 responses, suggesting a Th1 bias. However, the increase in IgG2 over IgG1 was less apparent when co-delivery of pCI-IL4 with pCI-GMCSF. Interestingly, the co-delivery of pCI-IL4 alone did not increase the IgG1 titre, suggesting that both pCI-GMCSF and pCI-IL4 are required for optimal IgG1 production. Thus, co-delivery of plasmid-encoded cytokine genes with in vivo electroporation has the ability to effectively modulate immune responses to a DNA vaccine in a large animal.

Animals↗

Comparative analysis of Marek's disease virus (MDV) glycoprotein-, lytic antigen pp38- and transformation antigen Meq-encoding genes: association of meq mutations with MDVs of high virulence.

Marek's disease (MD) is a highly contagious lymphoproliferative and demyelinating disorder of chickens. MD is caused by Marek's disease virus (MDV), a cell-associated, acute-transforming alphaherpesvirus. For three decades, losses to the poultry industry due to MD have been greatly limited through the use of live vaccines. MDV vaccine strains are comprised of antigenically related, apathogenic MDVs originally isolated from chickens (MDV-2), turkeys (herpesvirus of turkeys, HVT) or attenuated-oncogenic strains of MDV-1 (CVI-988). Since the inception of high-density poultry production and MD vaccination, there have been two discernible increases in the virulence of MDV field strains. Our objectives were to determine if common mutations in the major glycoprotein genes, a major lytic antigen phosphoprotein 38 (pp38) or a major latency/transformation antigen Meq (Marek's EcoRI-Q-encoded protein) were associated with enhanced MDV virulence. To address this, we cloned and sequenced the major surface glycoprotein genes (gB, gC, gD, gE, gH, gI, and gL) of five MDV strains that were representative of the virulent (v), very virulent (vv) and very virulent plus (vv+) pathotypes of MDV. We found no consistent mutations in these genes that correlated strictly with virulence level. The glycoprotein genes most similar among MDV-1, MDV-2 and HVT (gB and gC, approximately 81 and 75%, respectively) were among the most conserved across pathotype. We found mutations mapping to the putative signal cleavage site in the gL genes in four out of eleven vv+MDVs, but this mutation was also identified in one vvMDV (643P) indicating that it did not correlate with enhanced virulence. In further analysis of an additional 12 MDV strains, we found no gross polymorphism in any of the glycoprotein genes. Likewise, by PCR and RFLP analysis, we found no polymorphism at the locus encoding the pp38 gene, an early lytic-phase gene associated with MDV replication. In contrast, we found distinct mutations in the latency and transformation-associated Marek's EcoRI-Q-encoded protein, Meq. In examination of the DNA and deduced amino acid sequence of meq genes from 26 MDV strains (9 m/vMDV, 5 vvMDV and 12 vv+MDVs), we found distinct polymorphism and point mutations that appeared to correlate with virulence. Although a complex trait like MDV virulence is likely to be multigenic, these data describe the first sets of mutations that appear to correlate with MDV virulence. Our conclusion is that since Meq is expressed primarily in the latent/transforming phase of MDV infection, and is not encoded by MDV-2 or HVT vaccine viruses, the evolution of MDV virulence may be due to selection on MDV-host cell interactions during latency and may not be mediated by the immune selection against virus lytic antigens such as the surface glycoproteins.

Amino Acid Sequence↗

Characterization of the sigmaB-encoding genes of muscovy duck reovirus: sigmaC-sigmaB-ELISA for antibodies against duck reovirus in ducks.

The sigmaB/sigmaC-encoding genes of muscovy duck reovirus (DRV) S12 strain were cloned, sequenced, and expressed in Escherichia coli. The sigmaC-encoding gene of DRV showed only 21-22% identity to that of avian reovirus (ARV) at both nucleotide and amino acid level. The sigmaB-encoding gene of DRV comprised 1163bp with one open reading frame (ORF). The ORF comprised 1104bp and encoded 367 amino acids with a predicted molecular mass of 40.44 kDa. A zinc-binding motif and a basic amino acid motif were found within the predicted amino acid sequence of sigmaB. The identities between the S12 and ARV were 59.3-64.0% and 60.9-62.5%, respectively, at the nucleotide and deduced amino acid levels. Phylogenetic analysis of the sigmaB-encoding gene sequence indicated that S12 separated as a distinct virus relative to other avian strains. The expressed sigmaB/sigmaC fusion proteins in E. coli could be detected, approximately 45 and 50kDa, respectively, by duck anti-reovirus polyclonal serum. In addition, an ELISA (sigmaB-sigmaC-ELISA) using the expressed sigmaB-sigmaC proteins as coating antigen for detection of antibodies to DRV in ducks was developed. In comparison with the virus neutralization test and agar gel immuno-diffusion test (AGID), the sigmaB-sigmaC-ELISA showed perfect specificity and sensitivity. The sigmaB-sigmaC-ELISA did not react with the antisera to other duck pathogens, implying that these two proteins were specific in recognition of DRV antibodies. Taken together, the results demonstrated that sigmaB-sigmaC-ELISA was a sensitive and accurate method for detecting antibodies to DRV.

Amino Acid Sequence↗

Enhancement of the immunogenicity of DNA vaccine against infectious bursal disease virus by co-delivery with plasmid encoding chicken interleukin 2.

The immunoregulatory activity of a nonmammalian interleukin 2 (IL-2), chicken IL-2 (chIL-2), was investigated using a DNA vaccine against infectious bursal disease virus (IBDV) as a model. Coadministration of a plasmid encoding the VP2 gene of IBDV (pCI-VP2) and a plasmid encoding chicken IL-2 gene (pCI-chIL-2) enhances bursal protection against both the homologous IBDV strain ZJ2000 and the heterologous strain BC6/85 compared to administration of pCI-VP2 alone. Vaccination with pCI-VP2 alone induces low bursal protection against ZJ2000 and only protects chickens from clinical outbreaks and mortality, but not from bursal damage caused by BC6/85. Co-administration of the plasmid encoding the polyprotein gene of IBDV (pCI-VP2/4/3) and pCI-chIL-2 provides complete protection (15/15) against ZJ2000 and satisfactory protection (13/15) against BC6/85. In contrast, only 10 out of 15 chickens and 6 out of 15 chickens were protected against ZJ2000 and BC6/85, respectively, using the pCI-VP2/4/3 vaccination alone. A significant increase in the IBDV-specific neutralizing antibody response was also observed in chickens that received pCI-VP2/4/3 plus pCI-chIL-2 as compared with those that received the pCI-VP2/4/3 vaccination alone. By administrating different amounts of plasmid DNA, we confirmed that the pCI-chIL-2, but not the backbone plasmid pCI, contributes to increased immunoprotection of DNA vaccine against IBDV. These results strongly indicate that the efficacy of avian DNA vaccine can be modulated by co-administration of a plasmid encoding chIL-2.

Adjuvants, Immunologic↗

The murine cytomegalovirus M73.5 gene, a member of a 3' co-terminal alternatively spliced gene family, encodes the gp24 virion glycoprotein.

We have identified a novel family of five 3' co-terminal transcripts in murine cytomegalovirus (MCMV) arranged in a tail-to-tail orientation with respect to the MCMV glycoprotein H (gH) gene M75. They share the same exon 2 sequence but possess different exon 1 sequences. Two of these spliced transcripts (M73) encode the MCMV homolog of glycoprotein N (gN) entirely within exon 1. Two other transcripts designated M73.5 encode a previously described virion glycoprotein gp24 that shares its first 20 amino acids with gN, but which has another 64 amino acids encoded within exon 2. The fifth transcript, designated m60, has an 80-bp exon 1 near the MCMV oriLyt region 10.8 kb upstream of exon 2. Both MCMV M73.5 and m60 encode type II glycoproteins expressed at the cell surface. Their shared exon 2 coding sequences likely represent the highly conserved region of an as yet unidentified betaherpesvirus-specific glycoprotein species.

3T3 Cells↗