Herpes simplex virus 1 (HSV-1)- An Overview

Herpes simplex virus 1 (HSV-1) is a member of the Alphaherpesvirinae subfamily of the Herpesviridae family, a group of viruses that cause infections in humans and animals. HSV-1 is mainly responsible for oral and ocular infections, such as cold sores and keratitis, but can also cause genital herpes and encephalitis in some cases.

HSV-1 has a complex structure composed of four main components:

• A linear double-stranded DNA genome that encodes more than 100 genes and is about 152 kilobase pairs long. The genome is divided into two unique regions, long (UL) and short (US), that are flanked by inverted repeats. The genome also has terminal repeats at both ends.
• An icosahedral protein capsid that surrounds the genome and consists of 162 capsomeres, each made of six or five copies of a major capsid protein. The capsid also contains minor proteins that are involved in DNA packaging, maturation, and interaction with the tegument. The capsid has a diameter of about 100 nanometers.
• A tegument layer that fills the space between the capsid and the envelope. The tegument contains various viral proteins that have functions in viral replication, transcription, immune evasion, and virion assembly. Some of these proteins are VP16, which activates viral gene expression; VHS, which shuts off host protein synthesis; and UL41, which degrades host mRNA.
• An envelope that is derived from the host cell membrane and contains viral glycoproteins that mediate attachment and entry into host cells. HSV-1 encodes at least 11 glycoproteins, such as gB, gC, gD, and gH/gL, that have roles in binding to specific receptors, fusion with the cell membrane, structural stability, and immune escape. The envelope also has spikes of about 8 nanometers long that project from its surface.

The lipid part of the virus is derived from the nuclear membrane of the infected host cell . The lipid bilayer forms the outermost layer of the viral envelope, which surrounds the proteinaceous tegument and the icosahedral capsid. The lipid envelope is essential for viral entry and egress, as it mediates fusion with host cell membranes and protects the viral genome from degradation.

The lipid envelope contains various viral glycoproteins that project as spikes from the surface. These glycoproteins are involved in binding to specific host receptors, triggering membrane fusion, facilitating viral attachment and penetration, and modulating host immune responses . HSV-1 encodes at least 11 glycoproteins, namely gB, gC, gD, gE, gG, gH, gI, gK, gL, gM, and gN. Among them, gB, gD, and gH/gL are essential for membrane fusion, while gC, gE/gI, and gM/gN are involved in immune evasion.

The lipid composition of the viral envelope reflects that of the host nuclear membrane, but it may also be modified by viral proteins during infection. For example, HSV-1 protein pUL21 has been shown to alter ceramide levels and distribution in infected cells, which may affect membrane curvature and stability. The lipid envelope is also sensitive to environmental factors such as temperature and pH, which may influence its fluidity and permeability. Therefore, the lipid part of the virus plays a crucial role in HSV-1 infection and pathogenesis.

The HSV-1 genome is a single, linear molecule of double-stranded DNA approximately 152 kb in length. It is divided into two unique segments called long (U L ) and short (U S ). Short regions of repeated sequence (a/b/c and a’/b’/ c’) occur at the genome ends and between the L and S segments. As DNA is replicated, the L and S segments invert at a high rate creating a total of four genome isomers. The four occur at equal frequencies in most wild-type HSV-1 populations.

The virus contains double-stranded DNA genome and is linear with molecular weight of 125–240 kbp. The herpesvirus genome is large comprising of 60- 120 genes and encodes at least 100 different proteins. Of these, more than 35 polypeptides are involved in the structure of the virus particle and at least 10 are part of the viral envelope. Herpesviruses encode an array of virus-specific enzymes involved in nucleic acid metabolism, DNA synthesis, gene expression, and protein regulation (DNA polymerase, helicase-primase, thymidine kinase, transcription factors, protein kinases).

A striking feature of herpesvirus DNAs is their sequence arrangement possessing terminal and internal repeated sequences. On the basis of sequence arrangement it is divided into 6 types – A,B,C,D,E and F. Type E genome is found in Herpes Simplex virus. The termini of class E consist of two elements. The terminal sequences (ab and ca) are inserted in an inverted orientation separating the unique sequences into long (Ul) and short (Us) domains.

Herpes simplex virus 1 (HSV-1) is a common infection that can cause oral or genital herpes. It is transmitted by oral contact, such as kissing or sharing saliva-contaminated items, or by sexual contact. HSV-1 infection can be asymptomatic or cause recurrent blisters or ulcers that can be painful and distressing.

HSV-1 infection is widespread and affects people of all ages and regions. According to the World Health Organization (WHO), an estimated 3.7 billion people under age 50 (67%) globally have HSV-1 infection. The prevalence of HSV-1 varies by geographic location, age group, sex, and socioeconomic status. In general, HSV-1 infection is more common in low- and middle-income countries, where it is acquired at an early age, than in high-income countries, where it is acquired later in life. However, the epidemiology of HSV-1 is changing over time, with less exposure in childhood and more in adulthood, and less oral but more genital acquisition.

In the United States (US), HSV-1 seroprevalence (the proportion of people who have antibodies to the virus) declined from 59.4% in 1999–2000 to 48% in 2015–2016. This decline was observed across all age groups, sexes, races/ethnicities, and education levels. The decline was more pronounced among adolescents (14–19 years old), from 39% to 23.3%, and young adults (20–29 years old), from 45.9% to 33.9%. This suggests that fewer people are acquiring HSV-1 infection during childhood or adolescence.

However, the decline in HSV-1 seroprevalence also implies that more people are susceptible to HSV-1 infection later in life, when they become sexually active. This increases the risk of acquiring genital herpes caused by HSV-1, which has been reported to account for up to 50% of new cases of genital herpes in some populations. Genital herpes caused by HSV-1 has similar clinical manifestations and complications as genital herpes caused by HSV-2, such as painful lesions, psychological distress, increased risk of HIV acquisition and transmission, and neonatal herpes.

Therefore, HSV-1 epidemiology is undergoing a remarkable transition in the US and other high-income countries, with implications for public health and clinical practice. HSV-1 will persist as a widely prevalent infection, with ever-increasing genital disease burden. Prevention strategies, such as education, counseling, condom use, and antiviral therapy, are needed to reduce the transmission and impact of HSV-1 infection. Furthermore, research on the development of effective vaccines against HSV-1 is warranted to control this global health problem.

HSV-1 infection is transmitted orally through saliva . It is usually transmitted by oral contact, such as by kissing or by sharing of the toothbrushes or other saliva-contaminated items . The HSV infection can also occur following mouth-to-skin contact, with the virus entering through minor abrasions in the skin . Autoinoculation may also cause infection of the eye.

The virus is usually acquired in childhood or during sexual activity, either through oral–oral or oral–genital contact. HSV-1 infects epithelial cells and infection begins with the attachment of virus particles to susceptible cells. Virions interact with specific cell-surface receptors through glycoproteins that project from the viral envelope.

People who are sexually active can get genital herpes, a common sexually transmitted disease (STD), by having vaginal, anal, or oral sex with someone who has the infection. Oral herpes caused by HSV-1 can spread from the mouth to the genitals through oral sex. This is why some cases of genital herpes are due to HSV-1.

People can have repeated outbreaks over time (‘recurrences’). These are usually shorter and less severe than the first outbreak. However, most people with herpes have no symptoms or only mild symptoms. Many people aren’t aware they have the infection and can pass along the virus to others without knowing. Therefore, prevention measures such as using condoms and avoiding contact with active lesions are important to reduce the risk of transmission.

HSV-1 replicates its DNA in the nucleus of the infected cell, using both viral and cellular factors. The replication process can be divided into several steps:

• Entry and uncoating: HSV-1 enters the cell by binding to specific receptors on the plasma membrane and fusing its envelope with the membrane. The viral capsid is then released into the cytoplasm, where it transports the viral DNA to the nuclear pore complex. The viral DNA is then injected into the nucleus, where it circularizes and becomes accessible for transcription .
• Transcription: HSV-1 expresses its genes in a temporal and coordinated manner, producing three classes of mRNAs: immediate-early (IE), early (E), and late (L). The IE genes encode transcriptional regulators that activate the expression of E and L genes. The E genes encode enzymes that are required for DNA replication, such as DNA polymerase, helicase-primase, origin-binding protein, and thymidine kinase. The L genes encode structural proteins that are incorporated into the virion, such as capsid, tegument, and envelope proteins .
• DNA replication: HSV-1 initiates DNA replication at three origins of replication: two located in the unique long (UL) region and one in the unique short (US) region of the genome. The origin-binding protein (UL9) binds to the origin sequences and recruits the helicase-primase complex (UL5/UL8/UL52), which unwinds the DNA and synthesizes RNA primers. The DNA polymerase (UL30) and its processivity factor (UL42) then bind to the primers and elongate the DNA strands. The single-stranded DNA binding protein (ICP8) stabilizes the replication fork and facilitates strand exchange. The resulting DNA molecules are concatemeric, meaning they consist of multiple copies of the genome linked end-to-end .
• Recombination: HSV-1 also uses recombination as a mechanism to repair DNA damage, resolve replication intermediates, and generate genomic diversity. Recombination occurs between homologous sequences within or between viral genomes, mediated by viral and cellular proteins. The viral proteins involved in recombination include ICP8, UL12 (a nuclease), UL29 (a recombinase), and UL30. The cellular proteins involved in recombination include Rad51, Rad52, Mre11-Rad50-Nbs1 complex, and Bloom syndrome helicase .
• Assembly and egress: HSV-1 assembles its virions in the nucleus by encapsidating the linearized genomic DNA into preformed capsids. The capsids then acquire tegument proteins by budding into the inner nuclear membrane, forming primary enveloped virions. These virions then fuse with the outer nuclear membrane, releasing naked capsids into the cytoplasm. The capsids then acquire a secondary envelope by budding into vesicles derived from the trans-Golgi network or endosomes, which contain viral glycoproteins. These vesicles then fuse with the plasma membrane or are released by exocytosis, releasing mature infectious virions .

HSV-1 is spread by kissing or exchanging saliva. The virus is usually acquired in childhood or during sexual activity, either through oral–oral or oral–genital contact. HSV-1 infects epithelial cells and infection begins with the attachment of virus particles to susceptible cells. Virions interact with specific cell-surface receptors through glycoproteins that project from the viral envelope. The typical lesion produced by HSV is the vesicle, a ballooning degeneration of intra-epithelial cells, which contains infectious fluid. The base of the vesicle contains multinucleate cells (Tzanck cells) and infected nuclei contain eosinophilic inclusion bodies. The roof of the vesicle breaks down and an ulcer forms. This happens rapidly on mucous membranes and non-keratinizing epithelia; on the skin, the ulcer crusts over, forming a scab, and then heals.

Natural killer (NK) cells play a significant role in early defenses by recognizing and destroying HSV-infected cells. HSV shows three unique biological properties: neurovirulence, latency, and reactivation. After the infection at the local site of inoculation, virus then invades the local nerve ending; and is transported by retrograde axonal flow to the dorsal root ganglia, where it replicates further, and then undergoes latency. Primary HSV infections are usually mild; in fact most are asymptomatic. Latency means non replicating state and occurs in trigeminal ganglia. HSV does not replicate in latent stage except for a small RNA, called micro-RNA (encoded by a latency- associated viral gene) which maintains the latent infection and prevents cell death. Reactivation processes are still not clearly understood. It is suggested that HSV DNA passes along the nerve axon back to the nerve ending where infection of epithelial cells may occur. Not all reactivation will result in a visible lesion; there may be asymptomatic shedding of virus only detectable by culture or DNA detection methods.

The factors influencing the development of recrudescent lesions are not yet clearly identified. An increase of CD8+ T suppressor lymphocyte activity is common at the time of recurrences. Some mediators (e.g. prostaglandins), and a temporary decrease in immune effector cell function, particularly delayed hypersensitivity, may enhance spread of HSV. Certainly, the known triggers for recurrences are accompanied by a local increase in prostaglandin levels, and depression of cell-mediated immunity predisposes to herpes recurrence. It occurs naturally, and can be induced by a variety of stimuli such as ultraviolet light (sunlight), fever, trauma and stress. The interval between the stimulus and the appearance of a clinically obvious lesion is 2–5 days; this has been demonstrated regularly in patients undergoing neurological interference with their trigeminal ganglion, a common site of herpes latency.

HSV-1 infection can cause a variety of signs and symptoms depending on the site and severity of infection. The most common clinical manifestations are:

• Oral herpes: This is the typical cold sore or fever blister that appears on the lips or around the mouth. It is usually caused by a primary or recurrent HSV-1 infection. The lesions are painful, fluid-filled blisters that rupture and form ulcers. They heal in about 7 to 10 days without scarring. Oral herpes can also affect the gums, tongue, palate, and throat (gingivostomatitis) or the tonsils and pharynx (pharyngotonsillitis). These forms of oral herpes are more common in children and young adults and can be accompanied by fever, malaise, and swollen lymph nodes.

• Genital herpes: Although HSV-2 is the main cause of genital herpes, HSV-1 can also infect the genital area through oral-genital contact. Genital herpes caused by HSV-1 tends to have less frequent and less severe recurrences than HSV-2. The lesions are similar to oral herpes, but they occur on the penis, vulva, vagina, cervix, anus, or buttocks. They can cause pain, itching, burning, discharge, and dysuria .

• Keratoconjunctivitis: This is an infection of the eye that can affect the cornea (keratitis), the conjunctiva (conjunctivitis), or both. It can be caused by direct contact with HSV-1 lesions or by autoinoculation from other sites of infection. Keratoconjunctivitis can cause pain, redness, tearing, blurred vision, sensitivity to light, and eyelid swelling. If left untreated, it can lead to corneal scarring, ulceration, and blindness .

• Skin infections: HSV-1 can infect the skin through minor abrasions or direct contact with lesions. This can result in localized blisters or ulcers on various parts of the body. Some examples are herpetic whitlow (infection of the finger), herpes gladiatorum (infection of wrestlers due to skin-to-skin contact), and eczema herpeticum (severe infection of eczematous skin). Skin infections can be complicated by secondary bacterial infections or systemic dissemination .

• Encephalitis: This is a rare but life-threatening complication of HSV-1 infection that involves inflammation of the brain. It usually occurs in adults and is thought to result from reactivation of latent virus in the trigeminal ganglion and spread to the central nervous system. Encephalitis can cause fever, headache, confusion, seizures, focal neurological deficits, and coma. It has a high mortality rate and can cause permanent neurological damage .

• Neonatal herpes: This is a serious infection that affects newborns who acquire HSV-1 from their mothers during pregnancy, delivery, or postnatally. Neonatal herpes can affect the skin, eyes, mouth (SEM disease), the central nervous system (CNS disease), or multiple organs (disseminated disease). The signs and symptoms may include vesicular lesions, fever, irritability, lethargy, seizures, poor feeding, jaundice, and respiratory distress. Neonatal herpes has a high morbidity and mortality rate and requires prompt antiviral treatment .

  Laboratory Diagnosis of Herpes Simplex Virus 1 (HSV-1)

Laboratory diagnosis of HSV-1 infection is important for confirming the presence of the virus, differentiating it from HSV-2, and guiding the appropriate treatment and management. There are various methods available for diagnosing HSV-1, depending on the type of specimen, the stage of infection, and the availability of resources. These methods include:

• Culture test: This is the gold standard for detecting HSV in vesicular fluid, skin swabs, corneal scrapings, or other specimens. The specimen is inoculated into a cell culture medium and observed for cytopathic effects (CPE) caused by HSV replication. The CPE typically appear within 2-3 days and consist of rounding and ballooning of cells, formation of multinucleated giant cells, and intranuclear inclusion bodies. The virus can then be identified by neutralization test or immunofluorescence staining with specific antiserum .
• Antigen detection: This is a rapid and sensitive method for detecting HSV antigens in specimens such as vesicle fluid, tissue smears, or biopsies. The most common techniques are direct fluorescent antigen (DFA) detection and enzyme immunoassay (EIA). These techniques use monoclonal or polyclonal antibodies labeled with fluorescent dyes or enzymes to bind to HSV antigens and produce a visible signal .
• Antibody detection: This is a serological method for detecting antibodies to HSV in blood samples. Antibodies appear 4-7 days after the infection and peak in 2-4 weeks. Primary infection can be detected by determining the presence of IgM or the rising titre of IgG by enzyme-linked immunosorbent assay (ELISA), immunofluorescence test (IFT), or complement fixation test (CFT). Serological assays based on the type-specific antigens, glycoprotein G (gG), can differentiate between HSV-1 and HSV-2 .
• Molecular diagnosis: This is the most sensitive and specific method for detecting HSV DNA in various specimens such as vesicle fluid, skin swabs, corneal scrapings, tissue biopsies, cerebrospinal fluid (CSF), or blood. The most widely used technique is polymerase chain reaction (PCR), which amplifies a target region of HSV DNA and detects it by gel electrophoresis, hybridization probes, or real-time fluorescence. PCR can also differentiate between HSV-1 and HSV-2 by using type-specific primers or probes .

The choice of diagnostic method depends on several factors, such as the type and quality of specimen, the stage and severity of infection, the availability of laboratory facilities and personnel, the cost-effectiveness and turnaround time of the test, and the clinical relevance of the result .

Treatment options for Herpes simplex virus 1 (HSV-1)

There is no cure for HSV-1 infection, but antiviral medications can help reduce the severity and duration of symptoms, as well as the frequency of recurrences. Antiviral drugs work by inhibiting the viral DNA polymerase, which is essential for viral replication.

The most commonly used antiviral drugs for HSV-1 infection are acyclovir, valacyclovir, and famciclovir. These drugs can be taken orally or applied topically, depending on the site and type of infection. Oral antivirals are generally well tolerated, but may cause gastrointestinal side effects or headache. Topical antivirals may cause local irritation or allergic reactions.

The dosage and duration of antiviral treatment depend on several factors, such as the patient`s age, immune status, renal function, and type of infection. The following are some general guidelines for antiviral treatment of HSV-1 infection :

• For primary oral infection (gingivostomatitis or pharyngitis), oral acyclovir (15 mg/kg five times daily for seven days) or valacyclovir (20 mg/kg three times daily for five days) can be given to children. Adults can take oral acyclovir (400 mg five times daily for seven to 10 days), valacyclovir (1 g twice daily for seven to 10 days), or famciclovir (250 mg three times daily for seven to 10 days).
• For recurrent oral infection (cold sores), topical acyclovir (5% cream applied five times daily for four days) or penciclovir (1% cream applied every two hours while awake for four days) can be used at the first sign of prodrome or lesion. Oral antivirals can also be used for episodic treatment or suppressive therapy. For episodic treatment, oral acyclovir (800 mg three times daily for two days), valacyclovir (2 g twice daily for one day), or famciclovir (1500 mg once) can be taken within six hours of symptom onset. For suppressive therapy, oral acyclovir (400 mg twice daily), valacyclovir (500 mg once daily), or famciclovir (250 mg twice daily) can be taken daily for up to 12 months to reduce the frequency and severity of recurrences.
• For primary genital infection, oral acyclovir (400 mg three times daily for seven to 10 days), valacyclovir (1 g twice daily for seven to 10 days), or famciclovir (250 mg three times daily for seven to 10 days) can be given to reduce pain, viral shedding, and lesion healing time.
• For recurrent genital infection, oral antivirals can be used for episodic treatment or suppressive therapy. For episodic treatment, oral acyclovir (800 mg three times daily for two days), valacyclovir (500 mg twice daily for three days), or famciclovir (1000 mg twice daily for one day) can be taken within six hours of symptom onset. For suppressive therapy, oral acyclovir (400 mg twice daily), valacyclovir (500 mg once daily), or famciclovir (250 mg twice daily) can be taken daily for up to 12 months to reduce the frequency and severity of recurrences.
• For keratoconjunctivitis, topical trifluridine (1% drops applied every two hours while awake for up to 21 days) or ganciclovir (0.15% gel applied five times daily until healed) can be used to treat corneal ulcers. Oral acyclovir (400 mg five times daily for 10 days) or valacyclovir (500 mg three times daily for 10 days) can also be given to prevent recurrence and complications.
• For skin infections, such as herpetic whitlow or eczema herpeticum, oral acyclovir (800 mg five times daily for five to 10 days), valacyclovir (1 g three times daily for five to 10 days), or famciclovir (500 mg three times daily for five to 10 days) can be given to reduce viral shedding and lesion healing time.
• For meningitis/encephalitis, intravenous acyclovir (10 mg/kg every eight hours for 14 to 21 days) is the treatment of choice. Oral valacyclovir (2 g four times daily for 14 to 21 days) may be an alternative option in some cases.
• For neonatal herpes, intravenous acyclovir (20 mg/kg every eight hours for 14 to 21 days) is the treatment of choice.

In addition to antiviral treatment, supportive measures such as analgesics, hydration, and local care may help relieve symptoms and prevent secondary bacterial infections. Patients with HSV-1 infection should also be counseled about the risk of transmission to others and the importance of hygiene and prevention measures.

Prevention of Herpes simplex virus 1 (HSV-1)

There is no vaccine or cure for HSV-1 infection, but there are some ways to prevent or reduce the risk of getting or transmitting the virus.

• Avoid direct contact with oral or genital lesions, such as kissing or oral sex, when you or your partner have symptoms or signs of an outbreak.
• Use a barrier method, such as a condom or a dental dam, during oral sex, even if there are no visible sores. This can reduce the risk of HSV-1 transmission to the genitals, but it does not eliminate it completely.
• Avoid sharing personal items that may come in contact with saliva, such as toothbrushes, lip balms, utensils, or cups.
• Wash your hands frequently and thoroughly, especially after touching your mouth or genitals.
• If you have frequent or severe outbreaks of oral herpes, you may benefit from taking antiviral medication on a daily basis to suppress the virus and reduce the frequency and severity of recurrences. Talk to your healthcare provider about the best option for you.
• If you have genital herpes caused by HSV-1, you may also consider taking antiviral medication before having sex with a new partner, to lower the chance of passing the virus to them. However, this is not a guarantee that you will not transmit the virus, so you should still inform your partner about your infection and use condoms or dental dams during sex.

• If you are pregnant and have a history of genital herpes caused by HSV-1, you should inform your healthcare provider as soon as possible. You may need to take antiviral medication during the last trimester of pregnancy to prevent an outbreak at the time of delivery and reduce the risk of neonatal herpes, a serious condition that can affect the newborn baby. You may also need to have a cesarean delivery if you have active lesions at the time of labor.
  
  Therefore, it is important to seek medical attention if:

• A cold sore lasts longer than two weeks or does not respond to treatment.
• A cold sore spreads to other parts of the face or body, such as the eyes, nose, or genitals.
• A cold sore is accompanied by severe pain, fever, headache, or swollen lymph nodes.
• A pregnant woman has symptoms of genital herpes or a history of HSV-1 infection.
• A newborn baby shows signs of HSV infection, such as blisters, fever, irritability, or poor feeding.

HSV-1 infection can be managed with proper treatment and prevention strategies. However, it is not possible to completely eliminate the virus from the body. Therefore, people with HSV-1 infection should be aware of their status and inform their partners before engaging in intimate contact. They should also monitor their symptoms and seek medical advice when needed. By doing so, they can reduce the risk of complications and transmission of HSV-1 infection.

There is no cure for HSV-1 infection, but antiviral medications can help reduce the severity and duration of symptoms, as well as the frequency of recurrences. Antiviral drugs work by inhibiting the viral DNA polymerase, which is essential for viral replication.

The most commonly used antiviral drugs for HSV-1 infection are acyclovir, valacyclovir, and famciclovir. These drugs can be taken orally or applied topically, depending on the site and type of infection. Oral antivirals are generally well tolerated, but may cause gastrointestinal side effects or headache. Topical antivirals may cause local irritation or allergic reactions.

The dosage and duration of antiviral treatment depend on several factors, such as the patient`s age, immune status, renal function, and type of infection. The following are some general guidelines for antiviral treatment of HSV-1 infection :

• For primary oral infection (gingivostomatitis or pharyngitis), oral acyclovir (15 mg/kg five times daily for seven days) or valacyclovir (20 mg/kg three times daily for five days) can be given to children. Adults can take oral acyclovir (400 mg five times daily for seven to 10 days), valacyclovir (1 g twice daily for seven to 10 days), or famciclovir (250 mg three times daily for seven to 10 days).
• For recurrent oral infection (cold sores), topical acyclovir (5% cream applied five times daily for four days) or penciclovir (1% cream applied every two hours while awake for four days) can be used at the first sign of prodrome or lesion. Oral antivirals can also be used for episodic treatment or suppressive therapy. For episodic treatment, oral acyclovir (800 mg three times daily for two days), valacyclovir (2 g twice daily for one day), or famciclovir (1500 mg once) can be taken within six hours of symptom onset. For suppressive therapy, oral acyclovir (400 mg twice daily), valacyclovir (500 mg once daily), or famciclovir (250 mg twice daily) can be taken daily for up to 12 months to reduce the frequency and severity of recurrences.
• For primary genital infection, oral acyclovir (400 mg three times daily for seven to 10 days), valacyclovir (1 g twice daily for seven to 10 days), or famciclovir (250 mg three times daily for seven to 10 days) can be given to reduce pain, viral shedding, and lesion healing time.
• For recurrent genital infection, oral antivirals can be used for episodic treatment or suppressive therapy. For episodic treatment, oral acyclovir (800 mg three times daily for two days), valacyclovir (500 mg twice daily for three days), or famciclovir (1000 mg twice daily for one day) can be taken within six hours of symptom onset. For suppressive therapy, oral acyclovir (400 mg twice daily), valacyclovir (500 mg once daily), or famciclovir (250 mg twice daily) can be taken daily for up to 12 months to reduce the frequency and severity of recurrences.
• For keratoconjunctivitis, topical trifluridine (1% drops applied every two hours while awake for up to 21 days) or ganciclovir (0.15% gel applied five times daily until healed) can be used to treat corneal ulcers. Oral acyclovir (400 mg five times daily for 10 days) or valacyclovir (500 mg three times daily for 10 days) can also be given to prevent recurrence and complications.
• For skin infections, such as herpetic whitlow or eczema herpeticum, oral acyclovir (800 mg five times daily for five to 10 days), valacyclovir (1 g three times daily for five to 10 days), or famciclovir (500 mg three times daily for five to 10 days) can be given to reduce viral shedding and lesion healing time.
• For meningitis/encephalitis, intravenous acyclovir (10 mg/kg every eight hours for 14 to 21 days) is the treatment of choice. Oral valacyclovir (2 g four times daily for 14 to 21 days) may be an alternative option in some cases.
• For neonatal herpes, intravenous acyclovir (20 mg/kg every eight hours for 14 to 21 days) is the treatment of choice.

In addition to antiviral treatment, supportive measures such as analgesics, hydration, and local care may help relieve symptoms and prevent secondary bacterial infections. Patients with HSV-1 infection should also be counseled about the risk of transmission to others and the importance of hygiene and prevention measures.

There is no vaccine or cure for HSV-1 infection, but there are some ways to prevent or reduce the risk of getting or transmitting the virus.

• Avoid direct contact with oral or genital lesions, such as kissing or oral sex, when you or your partner have symptoms or signs of an outbreak.
• Use a barrier method, such as a condom or a dental dam, during oral sex, even if there are no visible sores. This can reduce the risk of HSV-1 transmission to the genitals, but it does not eliminate it completely.
• Avoid sharing personal items that may come in contact with saliva, such as toothbrushes, lip balms, utensils, or cups.
• Wash your hands frequently and thoroughly, especially after touching your mouth or genitals.
• If you have frequent or severe outbreaks of oral herpes, you may benefit from taking antiviral medication on a daily basis to suppress the virus and reduce the frequency and severity of recurrences. Talk to your healthcare provider about the best option for you.
• If you have genital herpes caused by HSV-1, you may also consider taking antiviral medication before having sex with a new partner, to lower the chance of passing the virus to them. However, this is not a guarantee that you will not transmit the virus, so you should still inform your partner about your infection and use condoms or dental dams during sex.

• If you are pregnant and have a history of genital herpes caused by HSV-1, you should inform your healthcare provider as soon as possible. You may need to take antiviral medication during the last trimester of pregnancy to prevent an outbreak at the time of delivery and reduce the risk of neonatal herpes, a serious condition that can affect the newborn baby. You may also need to have a cesarean delivery if you have active lesions at the time of labor.
  
  Therefore, it is important to seek medical attention if:

• A cold sore lasts longer than two weeks or does not respond to treatment.
• A cold sore spreads to other parts of the face or body, such as the eyes, nose, or genitals.
• A cold sore is accompanied by severe pain, fever, headache, or swollen lymph nodes.
• A pregnant woman has symptoms of genital herpes or a history of HSV-1 infection.
• A newborn baby shows signs of HSV infection, such as blisters, fever, irritability, or poor feeding.

HSV-1 infection can be managed with proper treatment and prevention strategies. However, it is not possible to completely eliminate the virus from the body. Therefore, people with HSV-1 infection should be aware of their status and inform their partners before engaging in intimate contact. They should also monitor their symptoms and seek medical advice when needed. By doing so, they can reduce the risk of complications and transmission of HSV-1 infection.

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