Benign type virus

If you are found to be infected with a common coronavirus E, NL63, OC43, and HKU1 , that does not mean you are infected with the novel coronavirus. There are different tests to determine if you are infected with novel coronavirus.

Your healthcare provider can determine if you should be tested. Types of coronaviruses Resources and references. Links with this icon indicate that you are leaving the CDC website. Linking to a non-federal website does not constitute an endorsement by CDC or any of its employees of the sponsors or the information and products presented on the website.

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The most widely used protocols use consensus primers that are directed at a highly conserved region of the L1 gene, since they are potentially capable of detecting all mucosal HPV types. Identification of more than 30 types can be achieved by hybridization with type-specific probes that can be performed in different formats and analysis of restriction-fragment length polymorphism by gel electrophoresis Bernard et al.

It is important to stress that, although the analytical sensitivity and specificity of these methods have been thoroughly compared see below , they may differ considerably in their ability to detect specific types present in multiple infections. For instance, Qu et al. In another comparison study, van Doorn et al. Because it amplifies a shorter fragment, it is considered to have a higher analytical sensitivity and a lower clinical specificity and to be adaptable for less well-preserved specimens.

This system has been licensed in Europe since This methodology has been shown to be reliable in detecting very high frequencies of known as well as new EV-HPV types in cutaneous lesions of renal transplant recipients. The release of fluorescence at each amplification cycle is directly proportional to the amount of amplicon generated and is therefore considered to be an accurate method for estimating viral load. A Taqman quantitative PCR system has been reported to assess HPV viral load, while controlling for variation in the cellular content of the sample by quantification of a nuclear gene.

Several reports indicated that a higher risk for cervical neoplasia was associated with higher viral loads of high-risk HPV types, in particular HPV 16 Swan et al. Although they showed that the risk for cervical neoplasia is associated with higher copy numbers of different HPV types Gravitt et al.

It is preferable to conclude that low viral copy numbers are associated with a low risk for developing CIN. However, further studies are warranted. Randomly labelled PCR products are then hybridized onto the chip, which is then scanned by laser fluorescence. In the case of multiple infections, multiple hybridization signals can be seen Kim, C. Despite its potential for further development, the utility of this system has not yet been demonstrated.

This is important for the identification of clinically relevant HPV infections. Moreover, the detection of such transcripts identified which high-risk HPV infections persisted without having to perform repeat testing Cuschieri et al. This reaction generates single-stranded RNAs to which specific molecular beacon probes can hybridize simultaneously to produce a fluorescent signal. The formation of newly generated RNA molecules is determined in real-time PCR by continuous monitoring of fluorescence in a fluorescent reader.

The rationale behind this method is that HPV genomes are often integrated into the host chromosomes in cervical cancers while, in normal and premalignant tissues, viral DNA is usually kept as episome. Using this assay, a strong correlation was shown between detection of integrated high-risk HPV transcripts and the presence of high-grade cervical neoplasia Klaes et al. This assay could provide a tool to predict disease progression and to monitor the efficacy of therapy Ziegert et al.

The main problem with these techniques is that RNA is more prone to degradation than DNA and is therefore less available in most biological specimens, depending on the time and type of storage conditions Habis et al. It was shown that the routine collection of specimens in liquid-based cytology solutions allows both morphological and immunohistochemical evaluations, and DNA and RNA studies can be performed for at least 14 days following sampling Tarkowski et al.

This may be especially true in cases of mixed infections where one type is present in large amounts. The two previous versions that had a low sensitivity have now been replaced by Hybrid Capture 2, one of the most extensively used HPV tests in both epidemiological settings and clinics. Hybrid Capture 2 is based on hybridization in solution of long synthetic RNA probes that are complementary to the genomic sequence of 13 high-risk 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68 and five low-risk 6, 11, 42, 43 and 44 HPV types and that are used to prepare high- B and low- A probe cocktails, which are applied in two separate reactions.

DNA present in the biological specimen is then hybridized in solution with each of the probe cocktails to allow the formation of specific HPV DNA—RNA hybrids, which are then captured by antibodies that are bound to the wells of a microtitre plate and that recognize them specifically. The immobilized hybrids are detected by a series of reactions that give rise to a luminescent product that can be measured in a luminometer. The intensity of emitted light, expressed as relative light units, is proportional to the amount of target DNA present in the specimen and provides a semiquantitative measure of the viral load.

Hybrid Capture 2 is currently available in a well microplate format, is easy to perform in clinical settings and can be automated. Furthermore, Hybrid Capture 2 does not require special facilities to avoid cross-contamination, because it does not rely on target amplification to achieve high sensitivity, as do PCR protocols. Often, only the high-risk cocktail is used; this reduces both the duration and cost of the test. The Food and Drug Administration has recommended a cut-off value for test-positive results of 1.

Peyton et al. The assay has been developed further to reduce cross-reactivity while maintaining sensitivity and for use either on DNA or RNA as targets. A recent comparison study concluded that, at the optimal cut-off points, Hybrid Capture 2 and 3 had similar screening performance characteristics for high-grade lesions diagnosed at the enrolment visit Castle et al.

For the analysis of HPV genomes, hybridization procedures in solid phase, such as southern blot for DNA and northern blot for RNA molecules, are excellent and can generate high-quality information; however, they are time-consuming and require large amounts of highly purified nucleic acids.

Moreover, they require well-preserved, full-size molecules and therefore cannot be carried out on all biological specimens, particularly not those derived from fixed tissues in which degradation of DNA is often observed. They are also technically cumbersome and are not suitable for large-scale population studies. In these techniques, high-molecular-weight, highly purified DNA is digested with different restriction endonucleases and is submitted to electrophoresis on agarose gels.

After denaturation, the DNA molecules are transferred to nitrocellulose or nylon filters, fixed and submitted to hybridization with specific HPV probes.

Depending on the label incorporated in the probes, different signal detection systems can be used. To increase the sensitivity of the test, radioactively labelled probes are commonly used, which limits the application of southern blot to certain laboratory conditions. Despite the stringent requirements, southern blot is considered to be the golden standard for the evaluation of HPV genomes, since it can identify HPV genomes in a specimen accurately and specifically; moreover, it determines the physical status of the genomes episomal or integrated and gives a semiquantitative measure of viral load.

In-situ hybridization is a technique by which specific nucleotide sequences are identified in cells or tissue sections with conserved morphology, which allows the precise spatial localization of target genomes in the biological specimen. One great advantage of in-situ hybridization is that it can be applied to routinely fixed and processed tissues, which overcomes the relatively low analytical sensitivity of this method.

Moreover, the integration status of HPV genomes can be inferred from the signal distribution in the nuclei of infected cell Mincheva et al.

In-situ hybridization has been used to detect messenger RNA mRNA as a marker of gene expression when levels of viral proteins are low Stoler et al. The major limitation of in-situ hybridization is the potential for errors in HPV typing because of probe cross-hybridization, but recent improvements enabled its use for the detection of HPV DNA and RNA in tissues with high sensitivities and specificities Birner et al. Moreover, detection of HPV 16 in cervical metastatic lymph nodes of head and neck cancer patients by in-situ hybridization was highly correlated with the localization of the primary tumour Begum et al.

Table 9 presents a comparison of HPV detection assays in clinical samples. An analysis of the intra- and inter-laboratory variability of these two PCR protocols Jacobs et al. Therefore, validated protocols, reagents and reference samples assure the best test performance in different settings.

It is very important to stress, however, that the analytical sensitivities and specificities of HPV tests vary largely, depending on assay characteristics, the type and quality of the biological specimen and the type and quality of the reagents used, including the use of different DNA polymerases that can affect test performance Castle et al. Moreover, caution should be used to interpret such comparisons, because the assays differ in their ability to detect different HPV types Kleter et al.

Current commercially available tests have been developed to detect the most common high-risk HPV types, as confirmed by a large series of epidemiological studies that included people from all over the world. Adaptation of the assays to include HPV types according to their geographical distribution should be considered as a means of increasing test specificity.

This is because several HPV infections do not persist and therefore do not lead to clinically relevant disease. Approaches to increase the clinical sensitivity of HPV assays that are being considered include: a testing only for the clinically relevant high-risk HPV types, b adding a viral load measure and c testing for high-risk HPV E6 and E7 transcripts.

Several studies have evaluated these and other possibilities, some of which are presented here. Continuous assessment and validation of current and new methodologies is essential for the evaluation of the carcinogenic risk of certain HPVs to humans. The antibody response to papillomaviruses is a key determinant of protective immunity. HPV serology is also an important epidemiological tool for the assay of past and present HPV infections and for the prediction of HPV-associated cancers and their precursor lesions.

Antibody responses to the HPV capsid are used as a marker of cumulative exposure to HPV while antibodies to E6 and E7 have been shown to be markers of malignant HPV-associated cervical or oropharyngeal disease. The development of serological assays was hampered initially by the lack of suitable cell culture systems to propagate papillomaviruses and to prepare infectious virions.

This has been overcome by recombinant DNA technologies that have allowed the generation of VLPs that display conformational, type-specific epitopes of purified, correctly folded early proteins such as E6 and E7 and of infectious pseudovirions that are suitable for neutralization assays. It has been shown by several groups that infection of cells with recombinant vaccinia viruses or baculoviruses that express the Ll with or without the L2 ORFs of HPV types 1, 6, 11 and 16 Zhou et al.

HPV 1 particles analysed by cryoelectron microscopy at a resolution of 3. For these assays, VLPs are usually produced by baculovirus expression in insect cells, purified by one or more rounds of equilibrium density or other ultra-centrifugations, adsorbed to plastic surfaces and used as antigens to bind capsid-specific antibodies.

In these tests, human antibodies compete for binding to VLPs that are adsorbed on plastic surfaces with a radio- or fluorescence-labelled monoclonal HPV type-specific reporter antibody directed to a dominant conformational epitope on the VLPs.

However, such competitive assays usually have lower analytical sensitivity compared with direct binding assays. In other approaches, monoclonal antibodies that recognize conformational VLP epitopes Hagensee et al. HPV L1 expressed in bacteria as the glutathione- S transferase GST fusion protein has been shown to form capsomers spontaneously, to display most epitopes defined on VLPs and to be suitable as an antigen for the detection of HPV capsid antibody Rose et al.

Recently, this type of assay has been adapted to fluorescent bead technology which allows the fast analysis of antibodies against many different theoretically up to proteins in parallel using only minute amounts of serum Chen et al. In view of the many papillomavirus types that potentially infect humans, this assay type could be of value in sero-epidemiological studies that analyse type-specific seroprevalences for large groups of HPV types simultaneously.

Several years of research were required to validate VLP-based ELISAs, and validation was laborious in the HPV system because: a early methods for the detection of HPV DNA were inaccurate, to the extent that misclassification seriously flawed early epidemiological studies of HPV Franco, ; b many of the more than different HPV types are not associated with malignancy and are not sexually transmitted, which renders serological cross-reactions difficult to predict on the basis of DNA homology; c most HPV infections are rapidly cleared spontaneously.

Thus, many people who test negatively for HPV DNA may have had a previous infection; d seroconversions can appear many months after infection see Section 1. In spite of these major theoretical difficulties, serology with viral capsids has shown an amazing concordance with detection of viral DNA at the cervix for several HPV types.

Human antibodies mostly recognize conformational epitopes on the capsid surface. HPV capsids can be disrupted, usually by treatment with high pH carbonate buffer, to destroy the type-specific epitopes; this results in the loss of type-specific serological reactivity, whereas cross-reactive antibody responses remain unaffected Carter et al.

It was also shown that neutralizing antibodies to HPV type 11 virions recognized conformational epitopes on synthetic HPV type 11 capsids.

An alternative method for assaying type-specific antibodies is based on the fact that they are usually present at higher titres than cross-reactive antibodies. Human anti-capsid antibody responses were found to be directed against epitopes on the Ll protein, because addition of L2 protein did not augment the association between HPV infection and antibody reactivity Carter et al. The sensitivity of assays is measured using panels of serum samples obtained from individuals with a documented infection with the virus in question, i.

State-of-the-art detection of viral DNA is not entirely straightforward, and misclassification is most commonly due to the inability to distinguish between some of the many viral genotypes, to contamination in PCR assays and to inadequate sampling. Persistence is a covariate of HPV seropositivity that may result from misclassification or may be a biological phenomenon.

A heavy infection may produce more viral protein that may induce a more effective antibody response. Alternatively, a weakly detectable presence of HPV DNA may be more commonly misclassified and not be due to true infection. The persistent presence of HPV DNA in samples taken at two different occasions from the same woman is more commonly associated with seropositivity than a transient presence of HPV DNA that was not detectable in a second sample taken from the same woman Wideroff et al.

Transient infections may not be present in the body long enough to evoke an antibody response. Alternatively, detection of HPV DNA that could not be repeated in a second sample may have been misclassified or may have reflected the presence of viral genomes that never resulted in an infection.

The HPV virion is stable and resistant to desiccation and remains extracellularly viable for at least 1 week Roden et al. Comparisons with women infected with other types of HPV are confounded by the fact that different carcinogenic genital types are transmitted similarly and that women in the high-risk group currently infected with a certain HPV type may have had previous infections with other HPV types. All serological studies of type specificity of the HPV capsid have found a strong type-restricted component, and, in a large population-based study performed in a population with a modest number of lifetime sexual partners, no covariation with the presence of other HPV types was found, which indicated type specificity Kjellberg et al.

Type specificity of HPV capsid-based assays is also supported by a very large number of experimental studies on immunological cross-reactivity of monoclonal antibodies against HPV capsids. Whereas disrupted or partially disrupted viruses expose epitopes that are broadly cross-reactive or even group specific Jenson et al.

The exceptions are HPV 6 and 11 that have been shown to contain shared epitopes and type-specific epitopes on intact capsids Christensen et al. The specificity of HPV capsid serology is also indicated by the fact that panels of serum samples taken from subjects with no or little sexual experience have very low seroprevalences see Section 1. Seroprevalence from different studies and laboratories must be compared with caution due to interlaboratory variation in assays and different definitions of cut-off.

Variation coefficients of 0. Especially important factors include the use of different groups of sera as a basis for determination of cut-off and different mathematical definitions of cut-off.

Neutralization assays are thought to be more type-specific than antibody-binding assays. Many neutralization assays are based on infectious pseudovirions Table While initial assays were technically complex and tedious, and were therefore restricted to the analysis of only small numbers of sera, they allowed the definition of neutralizing epitopes by monoclonal antibodies see also Section 1.

Recent developments suggest that the high-throughput analysis that is needed for large epidemiological and vaccination studies may be feasible. Antibodies to E6 and E7 proteins of HPV types 16 and 18 are markers of HPV-associated malignant disease but, since not all patients with tumours show such antibodies, they cannot be used as diagnostic markers. The association of E6 and E7 antibodies with cervical cancer was already apparent in initial studies that analysed only linear epitopes by either peptide ELISA or western blot analysis, despite the low sensitivity and specificity of these assays.

Methods that apply full-length E6 or E7 proteins that present conformational epitopes, i. ELISAs that use yeast-expressed biochemically purified and renatured full-length HPV 16 and 18 E6 and E7 proteins have been shown to be more specific and equally sensitive compared with radioimmunoprecipitation assays Meschede et al. Epidemiological studies using these assays have not yet been published. From studies that used linear epitopes as antigens in either peptide ELISA or western blot analysis, there is some indication that antibodies to E2 and E4 or some specific linear sequences of these proteins are associated with cervical cancer, but no consistent picture has emerged.

As seen for antibodies to L1 and also to E6 and E7 proteins, assays that use proteins that also present conformational epitopes need to be developed before this question can be analysed appropriately.

HPV is a prevalent pathogen, the epidemiology of which has mostly been studied in the uterine cervix and the vagina.

This section is therefore restricted to the natural history of genital HPV types. The cervical transformation zone can be considered as a ring of tissue that is susceptible to the carcinogenicity of HPV.

Cervical HPV infection can be assessed visually, microscopically via cytology or histology and by molecular detection methods. The basic steps that lead from the normal cervix to cancer are well established see Figure 8. To a large extent, these are probably also valid for the natural history of HPV in lesions at other anogenital sites; however, the molecular epidemiology of HPV infection at these sites is not as well characterized as that in the uterine cervix.

Natural history of preclinical abnormalities of the cervix. The major steps known to be necessary for cervical carcinogenesis include HPV infection, persistence of that infection, progression to precancerous lesions and eventually invasion. Provided that the latter step has not taken place, this process is reversible by the clearance of HPV infection and regression of precancer, which happen in many women who have ever experienced HPV infection.

As discussed below, HPV infection might usefully be separated into low-viral load infections that engender no microscopically evident abnormalities and higher-viral load infections that do.

As described in Section 1. Among the latter, approximately 15 are considered to be high-risk types. The various HPV types do not all occur in different populations at the same rate; therefore, although much is known about the epidemiology and natural history of HPV infections, little is known about the long-term characteristics of infections at the type-specific level, e. Most knowledge refers to HPV 16, which is the type most frequently found in tumours in the general population, and is discussed separately below.

The most common mode of horizontal transmission of anogenital HPV is by sexual activity through contact with infected cervical, vaginal, vulvar, penile or anal epithelium. In the early s, Barrett et al. Similar results have been reported by others Teokharov, ; Barrasso et al.

There is now overwhelming epidemiological evidence for the role of sexual activity in the transmission of anogenital HPV Franco et al. Studies among initially virginal women strongly confirm the sexually transmitted nature of HPV infection Rylander et al.

Sexual contact with an infected partner is necessary for transmission, presumably through microscopic abrasions in the mucosa or skin, and HPV infections are easily transmitted; however, on the basis of data on lesbians, it appears that intromissive intercourse in which an infected penis enters the vagina is not strictly necessary Marrazzo et al.

Moreover, transmission may take place in one anogenital site, such as the introitus, and the infection may be spread by self-inoculation to another site Winer et al. As a group, anogenital HPVs are the most common sexually transmitted infections but there is some evidence that the degree of sexual transmissibility may vary among types and across populations Franco et al.

Although fewer studies have been conducted on the prevalence of HPV infection among men than among women, HPV infections also appear to be common in men Baldwin et al. In the few studies that have evaluated factors associated with infection in men, sexual history, age and possibly condom use are associated with the prevalence of HPV Baldwin et al.

Published data on the natural history of HPV in men are scarce; however, several large prospective studies of HPV infection in men are currently being carried out.

As with any other sexually transmitted infection, prevention of HPV infection would greatly benefit from a better understanding of the determinants of transmission and infection among men.

HPV infections can be transmitted not only by peno-vaginal intercourse, but also by other sexual practices, e. Marrazzo et al. This review suggested that sexual practices between female sexual partners could result in transmission of HPV. Hand carriage of genital HPV types in patients with genital warts was identified by Sonnex et al. The non-sexual mode of transmission of genital HPV remains a controversial issue. However, a number of studies Pao et al.

Vertical transmission occurs when a parent conveys an infection to its unborn offspring, including a special form of vertical transmission — perinatal infection. Vertical transmission of HPV from mother to child was first suggested in the s Hajek, and was subsequently supported by several other studies Cason et al. Rare cases of anogenital warts in newborns have been reported Tang et al. Results from studies of transmission in infants are not consistent, and do not provide a clear indication of the rate of infection among neonates who are exposed perinatally.

Differences in samples and techniques may be the reasons for the variability and inconsistency in these results. Tenti et al. However, discordant mother—newborn pairs have been reported in several studies, as well as HPV-positive babies born to HPV-negative mothers and transmission of HPV by the transplacental route before delivery Puranen et al. Perinatal transmission of HPV has been demonstrated unequivocally for the rare disease juvenile respiratory papillomatosis Dillner et al.

Earlier studies of juvenile-onset recurrent respiratory papillomatosis in infants and young children indicated that HPV infections may be transmitted from mother to infant, probably at the time of delivery.

Age of the mother, birth order of the infant and mode of delivery are considered to be important determinants of transmission.

Most infants who develop juvenile-onset recurrent respiratory papillomatosis are the first-born single or twin infant of women who tend to be younger than other mothers who gave birth at the same institutions Kashima et al.

Cesarean delivery is generally thought to protect against perinatal transmission of HPV Tseng et al. Kosko and Derkay and Summersgill et al. It would be particularly valuable to confirm the prevalence of established HPV infections in babies after vaginal birth in the absence of convincing seroconversions using assays that provide specific although insensitive biomarkers of infection Dillner et al.

Even if anogenital infections with high viral load are rare in babies, exposure at birth could influence immune response later in life at the time of sexual exposure Mant et al.

In two large case series from Wuhan, Chen et al. A study from a network of Chicago area hospitals on patients found dizziness in Finally, from the reviews on the topic of dizziness it emerges that there is an important variability among studies [ 10 ], and even if dizziness is not uncommon in COVID, the studies are not sufficiently specific in order to define its vestibular origin [ 11 ].

About clinical reports, two cases of vestibular neuritis have been reported by Malayala and Raza [ 12 ] and Vanaparthy et al. Another two cases have been described by Mat et al. With a more specific and instrumental study on 41 patients, Gallus et al. Furthermore, despite the cited studies, COVIDrelated BPPV has not been described in the literature, even if it is the most common cause of peripheral vestibular vertigo. What is the exact cause of this relationship?

Alternatively, in cases of more serious infection, with hospitalization and intensive care recovery, immobilization and prolonged bed rest could lead to the development of BPPV. Another hypothesis could be related to the endothelial dysfunction involving cerebral venous hemodynamics; this mechanism is extremely interesting and it was also described for sudden hearing loss [ 16 ].

Finally, similarly to what happens in the central nervous system often involved in COVID [ 17 ], a direct effect of viral infection on the peripheral vestibular system, namely the otolitic membrane, could justify the onset of vertigo.

In this topic, a direct cytopathic effect of the virus, an inflammatory response, a cytokine storm or a vascular event could be proposed as pathogenetic factors.

A final consideration concerns the unusually high proportion of horizontal canal involvement in our series compared to the typical distribution of BPPV subtypes.

We found horizontal canal involvement in two out of three patients admitted to intensive care. As it is well known, these patients are often placed in pronation to improve oxygenation, and this forced position could modify the course of positional vertigo, justifying a greater incidence of forms involving the horizontal canal in our series.

In conclusion, further studies are necessary to investigate the effects of COVID, as well as for understanding long-term risks, on the vestibular system. In particular, studies on a large series of patients are needed to better evaluate the prevalence and pathophysiological mechanisms underlying BPPV in these patients. The topics of future investigation can make use of instrumental techniques that allow for better study of the involvement of different components of vestibular system.

Conceptualization: P. All authors have read and agreed to the published version of the manuscript. The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of Fondazione Policlinico Universitario A. National Center for Biotechnology Information , U. Journal List Audiol Res v. Audiol Res. Published online Aug